Research - Arterial Disease / Atherosclerosis / Arteriosclerosis
Sleep modulates haematopoiesis and protects against atherosclerosis
Cameron S. McAlpine, Máté G. Kiss, Sara Rattik, Shun He, Anne Vassalli, Colin Valet, Atsushi Anzai, Christopher T. Chan, ohn E. Mindur, Florian Kahles, Wolfram C. Poller, Vanessa Frodermann, Ashley M. Fenn, Annemijn F. Gregory, Lennard Halle, Yoshiko Iwamoto, Friedrich F. Hoyer, Christoph J. Binder, Peter Libby, Mehdi Tafti, Thomas E. Scammell, Matthias Nahrendorf & Filip K. Swirski
Sleep is integral to life1. Although insufficient or disrupted sleep increases the risk of multiple pathological conditions, including cardiovascular disease2, we know little about the cellular and molecular mechanisms by which sleep maintains cardiovascular health. Here we report that sleep regulates haematopoiesis and protects against atherosclerosis in mice. We show that mice subjected to sleep fragmentation produce more Ly-6Chigh monocytes, develop larger atherosclerotic lesions and produce less hypocretin—a stimulatory and wake-promoting neuropeptide—in the lateral hypothalamus. Hypocretin controls myelopoiesis by restricting the production of CSF1 by hypocretin-receptor-expressing pre-neutrophils in the bone marrow. Whereas hypocretin-null and haematopoietic hypocretin-receptor-null mice develop monocytosis and accelerated atherosclerosis, sleep-fragmented mice with either haematopoietic CSF1 deficiency or hypocretin supplementation have reduced numbers of circulating monocytes and smaller atherosclerotic lesions. Together, these results identify a neuro-immune axis that links sleep to haematopoiesis and atherosclerosis.
Source : Journal Nature
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Protective effect of Urtica dioica leaf hydro alcoholic extract against experimentally-induced atherosclerosis in rats
Fatemeh Namazi,1 Tahoora Shomali,2,* Pouya Taghikhani,2 and Saied Nazifi
Finding compounds that could be used for prevention of atherosclerosis (AS) is highly desired. The present study evaluated the protective effects of Urtica dioica (UD, commonly known as stinging nettle) leaf ethanolic extract against high-fat diet-induced AS in rats.
Materials and Methods:
In this study, 40 male adult Sprauge-Dawley rats were randomly allocated to 4 equal groups and treated as follows for 9 consecutive weeks: (1) Normal control (NC; normal rats that were fed with a basic diet); (2) Atherosclerotic rats (AT; which received no particular treatment); (3) Atherosclerotic rats that received 100 mg/kg/day ethanolic extract of UD orally and (4) Atherosclerotic rats that received simvastatin 4 mg/kg/day orally. Atherosclerosis was induced by a high-fat diet accompanied by propylthiouracil and vitamin D3.
Marked hypercholesterolemia and significant increase in LDL-C/HDL-C ratio were observed in rats of AT group. Administration of UD significantly reduced these parameters as compared to AT group (p<0.05 for all cases). In histopathological evaluations of the aortic arch, AT rats showed atherosclerotic lesions, which were markedly ameliorated in rats treated with UD or simvastatin. Simvastatin and UD significantly reduced medial (p<0.05) but not intimal thickness. Increased level of malondialdehyde (MDA) and reduced total antioxidant capacity (TAC) were observed in the aortic arch of AT rats (p<0.05 for all cases). In contrast with simvastatin, UD extract had no significant effect on these parameters.
Ethanolic extract of UD prevents establishment of atherosclerotic lesions in rat aorta, which is associated with positive effects on serum lipid profile without significantly affecting antioxidant status.
Source : Avicenna Journal of Phytomedicine
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Herbal composition of Cinnamomum cassia, Pinus densiflora, Curcuma longa and Glycyrrhiza glabra prevents atherosclerosis by upregulating p27 (Kip1) expression
- Jung-Jin Lee,
- Ji-Hye Lee,
- Won-Kyung Cho,
- Joo-Hui Han and
- Jin Yeul Ma
Background Kiom-18 is a novel composition of Cinnamomum cassia, Pinus densiflora, Curcuma longa and Glycyrrhiza glabra. Curcuma longa and Glycyrrhiza glabra, which are traditional medicines in Asia, have been reported to demonstrate preventive effects against atherosclerosis; however, they have not yet been developed into functional atherosclerosis treatments. We therefore studied the anti-atherosclerotic effects and possible molecular mechanisms of Kiom-18 using vascular smooth muscle cells (VSMCs).
MethodsTo assess the anti-proliferative effect of Kiom-18 in vitro, we performed thymidine incorporation, cell cycle progression, immunoblotting and immunofluorescence assays in VSMCs stimulated by platelet derived-growth factor (PDGF)-BB. In addition, we used LDLr knockout mice to identify the effects of Kiom-18 as a preliminary result in an atherosclerosis animal model.
Results Kiom-18 inhibited platelet-derived growth factor (PDGF)-BB-stimulated-VSMC proliferation and DNA synthesis. Additionally, Kiom-18 arrested the cell cycle transition of G0/G1 stimulated by PDGF-BB and its cell cycle-related proteins. Correspondingly, the level of p27kip1 expression was upregulated in the presence of the Kiom-18 extract. Moreover, in an atherosclerosis animal model of LDLr knockout mice, Kiom-18 extract showed a preventive effect for the formation of atherosclerotic plaque and suppressed body weight, fat weight, food treatment efficiency, neutrophil count, and triglyceride level.
Conclusions These results indicate that Kiom-18 exerts anti-atherosclerotic effects by inhibiting VSMC proliferation via G0/G1 arrest, which upregulates p27Kip1 expression.
Source BMC Complementary and Alternative Medicine
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Wen-Xin Decoction ameliorates vascular endothelium dysfunction via the PI3K/AKT/eNOS pathway in experimental atherosclerosis in rats
- Tongda Li†,
- Dongmei Li†,
- Hui Xu,
- Huamin Zhang,
- Danli Tang and
- Hongxin Cao
Nitric oxide (NO) is the most powerful vasodilator that inhibits leukocyte adhesion, platelet aggregation, and vascular smooth muscle cell proliferation. However, excessive NO can cause lipid peroxidation and direct endothelial cell damage. Therefore, investigation of the role of NO in artherosclerosis development is important. Wen-Xin Decoction (WXD) has been shown to relieve myocardial ischemia reperfusion injury and prevent leukocyte adhesion and invasion; in addition, it can accelerate angiogenesis and prevent platelet activation and aggregation. In this study, we focused on the NO pathway to further clarify the protective effects of WXD on the vascular endothelium in rat models of artherosclerosis.
Wistar rats were randomly divided into a normal group (n = 10) and a model group (n = 75). Rat models of atherosclerosis were generated by intraperitoneal vitamin D3 (3 months) injections and administration of a high-fat diet (3 months with vitamin D3 and 2 months alone). The model rats were randomly divided into five groups (n = 15 each): model (saline), atorvastatin (4.8 mg/kg/d atorvastatin), high-dose WXD (9 g/kg/d), medium-dose WXD (4.5 g/kg/d), and low-dose WXD (2.25 g/kg/d) groups. Each group received continuous drug or saline administration (suspended liquid gavage) for 30 days, following which all animals were sacrificed. The ultrastructure and histopathological changes of vascular endothelial cells and the expression of PI3K/AKT/eNOS and iNOS in the thoracic aorta tissue were analyzed.
WXD increased NO levels, modulated the NO/ET-1 ratio, and promoted repair of the injured vascular endothelium in a dose-dependent manner. At a high dose, WXD regulated the NO/ET-1 ratio as effectively as atorvastatin; furthermore, it increased NO levels within the physiological range to prevent endothelial damage caused by excessive NO expression. Real-time polymerase chain reaction and Western blot analysis showed that WXD significantly upregulated the mRNA and protein expressions of PI3K, AKT, and eNOS mRNA and significantly increased AKT and eNOS phosphorylation.
ConclusionsOur results suggest that WXD protects and maintains the integrity of the vascular endothelium by activating the PI3K/AKT/eNOS pathway, decreasing iNOS expression, and promoting the release of physiological NO levels.
Source : BMC Complementary and Alternative Medicine
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Inhibitory Effect of a French Maritime Pine Bark Extract-Based Nutritional Supplement on TNF-α-Induced Inflammation and Oxidative Stress in Human Coronary Artery Endothelial Cells
Kristine C. Y. McGrath,1 Xiao-Hong Li,1,2 Lucinda S. McRobb,3 and Alison K. Heather4
Oxidative stress and inflammation, leading to endothelial dysfunction, contribute to the pathogenesis of atherosclerosis. The popularity of natural product supplements has increased in recent years, especially those with purported anti-inflammatory and/or antioxidant effects. The efficacy and mechanism of many of these products are not yet well understood. In this study, we tested the antioxidant and anti-inflammatory effects of a supplement, HIPER Health Supplement (HIPER), on cytokine-induced inflammation and oxidative stress in human coronary artery endothelial cells (HCAECs). HIPER is a mixture of French maritime pine bark extract (PBE), honey, aloe vera, and papaya extract. Treatment for 24 hours with HIPER reduced TNF-α-induced reactive oxygen species (ROS) generation that was associated with decreased NADPH oxidase 4 and increased superoxide dismutase-1 expression. HIPER inhibited TNF-α induced monocyte adhesion to HCAECs that was in keeping with decreased expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1 and decreased nuclear factor-kappa B (NF-κB) activation. Further investigation of mechanism showed HIPER reduced TNF-α induced IκBα and p38 and MEK1/2 MAP kinases phosphorylation. Our findings show that HIPER has potent inhibitory effects on HCAECs inflammatory and oxidative stress responses that may protect against endothelial dysfunction that underlies early atherosclerotic lesion formation.
Source : Evidence Based Complementary and Alternative Medicine
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Effect of Shoushen granule on arterial elasticity in patients with carotid atherosclerosis: a clinical randomized controlled trial
Objective To investigate the effectiveness of Shoushen granule, Chinese herbal preparation, on carotid artery elasticity in patients with carotid atherosclerosis.
Methods The total of 156 carotid atherosclerosis patients were randomly divided into the intervention group (83 cases, treated with Shoushen granule) and the control group (73 cases, treated with pravastatin). Brachial-ankle pulse wave velocity (baPWV) and Ankle-Brachial Pressure Index (ABI) were measured by automated arteriosclerosis detector. The changes of common carotid artery intima-media thickness (IMT) and parameters of the carotid artery elasticity in patients, including stiffness parameter (β), pressure-strain elastic modulus (Ep), arterial compliance (Ac), augmentation index (AI), and pulse wave velocity β (PWVβ) were detected by Echo-Tracking (ET) technique before and after 24 week treatment. In the meantime, levels of blood lipid, and liver and renal function were measured respectively.
Results After 24 weeks, baPWV, IMT and parameters of the carotid artery elasticity (β, Ep, AI and PWVβ) were markedly decreased in intervention group compared with those of before treatment (P < 0.01), but the level of Ac was increased significantly (P < 0.01). And there were no significant differences compared with control group on the same period (P > 0.05).
Conclusion In this pilot study, it was demonstrated ET technology and automated arteriosclerosis detector could be used to evaluate carotid artery elasticity effectively, and the action of Shoushen granule on carotid atherosclerosis might be related to the regulation of carotid artery elasticity.
Source : Journal of Traditional Chinese Medicine
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Pomegranate-Date Cocktail a Day Keeps the Dr. Away
Study shows pomegranate juice/date combo fights heart disease
Glorious, red pomegranates and their Middle Eastern sister, luscious toffee-like dates, are delicious, increasingly trendy, and healthy to boot. As it turns out, when consumed together they are a winning combination in the war against heart disease. Just half a glass of pomegranate juice a day with a handful of dates can do the trick!
A team of researchers at the Technion-Israel Institute of Technology, led by Professor Michael Aviram of the Rappaport Faculty of Medicine and Rambam Medical Center, has discovered that the combination of pomegranate juice and dates along with their pits provide maximum protection against atherosclerosis (plaque buildup or hardening of the arteries), which can cause a heart attack or stroke. The findings were published in the most recent issue (March 26, 2015) of Food & Function, a journal of The Royal Society of Chemistry.
A number of risk factors are involved in the development of atherosclerosis, including cholesterol oxidation, which leads to accumulation of lipids in the arterial wall. Natural antioxidants can slow down the oxidation process in the body, and serve to reduce the risk of heart attack. For the past 25 years, Prof. Aviram and his research team have been working on isolating and researching those antioxidants, in order to keep plaque buildup at bay.
Going into the most recent study, the team was aware of the individual benefits provided by pomegranates and dates. Pomegranate juice, rich in polyphenolic antioxidants (derived from plants), has been shown to most significantly reduce oxidative stress. Dates, which are rich sources of phenolic radical scavenger antioxidants, also inhibit the oxidation of LDL (the so-called “bad cholesterol”) and stimulate the removal of cholesterol from lipid-laden arterial cells. Prof. Aviram had a hunch that since dates and pomegranate juice are composed of different phenolic antioxidants, the combination could thus prove more beneficial than the sum of its parts.
In a trial performed on arterial cells in culture, as well as in atherosclerotic mice, the Technion team found that the triple combination of pomegranate juice, date fruits and date pits did indeed provide maximum protection against the development of atherosclerosis because the combination reduced oxidative stress in the arterial wall by 33% and decreased arterial cholesterol content by 28%.
The researchers conclude that people at high risk for cardiovascular diseases, as well as healthy individuals, could benefit from consuming the combination of half a glass of pomegranate juice (4 ounces), together with 3 dates. Ideally, the pits should be ground up into a paste and eaten as well, but even without the pits, the combination is better than either fruit alone.
Source : Newswise
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The protective effect of the Cornus mas fruits (cornelian cherry) on hypertriglyceridemia and atherosclerosis through PPAR[alpha] activation in hypercholesterolemic rabbits.
Cornelian cherry (Cornus mas L.) fruits have been used in traditional cuisine and in folk medicine in various countries. This study was conducted to evaluate the constituents and impact of cornelian cherry (C. mas L.) fruits lyophilisate on lipid levels, PPAR[alpha] protein expression, atheromatous changes in the aorta, oxidoredox state, and proinflammatory cytokines in hypercholesterolemic rabbits. The HPLC-MS method was used for determining active constituents in cornelian cherry. In a subsequent in vivo study the protective effect of the cornelian cherry on diet-induced hyperlipidemia was studied using a rabbit model fed 1% cholesterol. Cornelian cherry (100 mg/kg b.w.) or simvastatin (5 mg/kg b.w.) were administered orally for 60 days. Two iridoids--loganic acid and cornuside--and five anthocyanins were identified as the main constituents of the cornelian cherry. The administering of the cornelian cherry led to a 44% significant decrease in serum triglyceride levels, as well as prevented development of atheromatous changes in the thoracic aorta. Cornelian cherry significantly increased PPAR[alpha] protein expression in the liver, indicating that its hypolipidemic effect may stem from enhanced fatty acid catabolism. Simvastatin treatment did not affect PPAR-[alpha] expression. Moreover, the cornelian cherry had a significant protective effect on diet- induced oxidative stress in the liver, as well as restored upregulated proinflammatory cytokines serum levels. In conclusion, we have shown loganic acid to be the main iridoid constituent in the European cultivar of the cornelian cherry, and proven that the cornelian cherry could have protective effects on diet-induced hypertriglicerydemia and atherosclerosis through enhanced PPAR[alpha] protein expression and via regulating oxidative stress and inflammation.
Source : International Journal of Phytotherapy and Phytopharmacology via Free Library
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Dark Chocolate Intake Improves Walking Distance and Walking Time in Patients with Peripheral Artery Disease
Loffredo L, Perri L, Catasca E, et al. Dark chocolate acutely improves walking autonomy in patients with peripheral artery disease. J Am Heart Assoc. July 2014;3(4). pii: e001072. doi: 10.1161/JAHA.114.001072.
More than a fifth of adults older than 70 years are affected by peripheral arterial disease (PAD) in Western countries.1 A major symptom of the disease is intermittent claudication (IC), pain caused by impaired blood flow to the limbs during physical exercise. Reduced blood flow in patients with PAD is the result of endothelial dysfunction, reduced glucose oxidation, accumulation of toxic metabolites, impaired nitric oxide (NO) generation, and/or oxidative stress. In an earlier study,2 oxidative stress resulted in impaired walking distance autonomy (WDA), while inhibiting oxidative stress led to improved maximal walking distance (MWD). Polyphenol-rich cocoa (Theobroma cacao) has been associated with artery dilatation by reducing oxidative stress and increasing NO generation.3,4 In particular, dark chocolate enhances artery dilatation by lowering the activation of NOX2, a subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which has been shown to exert vasoconstrictor activity in both animals and humans. These authors conducted an interventional, crossover, single-blinded study to measure the acute effect of dark chocolate on WDA, artery dilatation, and NOX2-mediated oxidative stress in patients affected by moderate-to-severe PAD.
Specifically, the trial investigated the acute effect of 40 g chocolate (dark vs. milk) on MWD, maximal walking time (MWT), ankle brachial index (ABI) at rest and postexercise, flow-mediated dilatation (FMD), oxidative stress, and NO generation. Oxidative stress was assessed through blood levels of NOX-2 derivative peptide (sNOX2-dp; a marker of NOX2 activation) and isoprostanes. Serum levels of nitrite-nitrate (NOx) were used to evaluate NO generation.
The study, conducted between January 2012 and September 2013, included 20 patients with PAD with IC. At baseline, all patients underwent a full medical history and physical examination and answered a questionnaire about their fruit and vegetable intake. They were randomly assigned to receive either 40 g dark chocolate (≥85% cocoa) or milk chocolate (≤35% cocoa) in a crossover design, with at least 1 week separating the 2 intervention phases. The modified Folin-Ciocalteu colorimetric method used to determine the polyphenol content of the chocolate revealed a significantly higher total and single polyphenol content in the dark compared with the milk chocolate (P<0.001).
On study visit days, fasting blood samples were collected, followed by the first ABI and FMD at rest. The patients then completed the first treadmill test, after which MWD and MWT were measured and postexercise ABI was performed. The patients consumed 40 g of dark or milk chocolate. Two hours later, blood samples were again collected to analyze oxidative stress markers and epicatechin levels, and a second ABI and FMD evaluation was conducted. After 20 minutes, each patient completed a second treadmill test to determine MWD and MWT, followed by another postexercise ABI.
Compared with baseline, no difference was observed 2 hours after milk chocolate consumption in serum epicatechin, its metabolite EC-3-O-methylether, or epigallocatechin-3-gallate (EGCG) levels; however, the levels of serum catechin increased significantly. Two hours after dark chocolate intake, serum levels of epicatechin and its metabolite EC-3-O-methylether, catechin, and EGCG increased compared with baseline values.
Compared with baseline, MWD and MWT increased after dark chocolate intake (P<0.001 for both) but not after milk chocolate intake. This is a novel finding, according to the authors, noting that it supports the hypothesis that polyphenol content may be responsible for this effect, as dark chocolate is richer in polyphenols than milk chocolate.5
In a within-group analysis, no significant effect on ABI at rest or after exercise was observed after dark or milk chocolate intake. The analysis of variance performed on the study data revealed a significant difference for treatments in FMD (P=0.003); sNOX2-dp release (P=0.04); serum 8-iso-prostaglandin F2α-III, an indicator of lipid peroxidation (P=0.018); MWD (P=0.01); MWT (P=0.006); and postexercise ABI (P=0.04).
Pairwise comparisons showed that sNOX2-dp (P<0.001) and serum isoprostanes (P=0.01) significantly decreased after dark chocolate consumption but not after milk chocolate intake. FMD (P<0.001) and NOx(P=0.001) increased after dark chocolate intake, but no changes were observed after milk chocolate intake.
Performing a multiple linear regression analysis using a forward selection, the authors report "that Δ of MWD was independently associated with Δ of MWT (P<0.001) and Δ of NOx (P=0.018)."
The authors conducted an accompanying in vitro study in which human umbilical vein endothelial cells (HUVECs) were cultured to analyze the effect of scalar doses of single polyphenols such as epicatechin, catechin, or EGCG or a mixture of those on HUVEC activation. They found that HUVECs incubated with a mixture of polyphenols significantly increased NO (P<0.001). Significant decreases were seen in levels of E-selectin (P<0.001) and soluble vascular adhesion molecule-1 (P<0.001) (both associated with cardiovascular disease risk).
The vasodilating effect of dark chocolate could be due to the antioxidant effect of its polyphenols, which has been documented in humans through reduction of oxidative stress markers and an increase in its plasma antioxidant property. In this study, the patients who consumed dark chocolate experienced short-term changes in oxidative stress elicited by reduced serum isoprotanes, reduced NOX2 activity, and enhanced generation of NO. "These data may lead to speculation that the enhanced NO generation could be responsible for artery dilatation and eventually improve WDA," write the authors.
Referring to the study's limitations, the authors suggest that although the study is useful in understanding the mechanism of disease related to IC, the results are not transferable to clinical practice because of the small sample size and study design (single-blinded with no placebo group). Also, they say, only indirect evidence suggests that vasodilation is the mechanism behind the increase in walking autonomy; a direct analysis of peripheral circulation was not done.
"The results of this study suggest that short-term administration of dark chocolate improves walking autonomy with a mechanism involving its high content of polyphenols and perhaps mediated by an oxidative stress mechanism, which ultimately leads to enhanced NO generation." A longer duration of dark chocolate intake should be studied to assess whether it could be used to treat IC in patients with PAD.
Source : American Botanical Council
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Homocysteine, vitamin B12 and folate levels in premature coronary artery disease
Saeed Sadeghian1*, Faramarz Fallahi2, Mojtaba Salarifar3, Gholamreza Davoodi1, Mehran Mahmoodian4, Nader Fallah5, Soodabeh Darvish4, Abbasali Karimi6 and Tehran Heart Center
1 Assistant Professor of Cardiology, Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
2 Assistant Professor of Cardiology, Shahed University, Tehran, Iran
3 Assistant Professor of Interventional Cardiology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
4 Researcher, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
5 Regular member of board, Department of Biostatistics, Shahed University, Tehran, Iran
6 Associated Professor of cardiac surgery, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
Background Hyperhomocysteinemia is known as an independent risk factor of atherosclerosis, but the probable role of hyperhomocysteinemia in premature Coronary Artery Disease (CAD) is not well studied. The aim of this study was to assess the role of hyperhomocysteinemia, folate and Vitamin B12 deficiency in the development of premature CAD.
Methods We performed an analytical case-control study on 294 individuals under 45 years (225 males and 69 females) who were admitted for selective coronary angiography to two centers in Tehran.
Results After considering the exclusion criteria, a total number of 225 individuals were enrolled of which 43.1% had CAD. The mean age of participants was 39.9 +/- 4.3 years (40.1 +/- 4.2 years in males and 39.4 +/- 4.8 years in females). Compared to the control group, the level of homocysteine measured in the plasma of the male participants was significantly high (14.9 +/- 1.2 versus 20.3 +/- 1.9 micromol/lit, P = 0.01). However there was no significant difference in homocysteine level of females with and without CAD (11.8 +/- 1.3 versus 11.5 ± 1.1 micromol/lit, P = 0.87). Mean plasma level of folic acid and vitamin B12 in the study group were 6.3 +/- 0.2 and 282.5 +/- 9.1 respectively. Based on these findings, 10.7% of the study group had folate deficiency while 26.6% had Vitamin B12 deficiency. Logistic regression analysis for evaluating independent CAD risk factors showed hyperhomocysteinemia as an independent risk factor for premature CAD in males (OR = 2.54 0.95% CI 1.23 to 5.22, P = 0.01). Study for the underlying causes of hyperhomocysteinemia showed that male gender and Vitamin B12 deficiency had significant influence on incidence of hyperhomocysteinemia.
Conclusion We may conclude that hyperhomocysteinemia is an independent risk factor for CAD in young patients (bellow 45 years old) – especially in men -and vitamin B12 deficiency is a preventable cause of hyperhomocysteinemia.
Source : BMC Cardiovascular Disorders
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Pycnogenol® and Centella Asiatica for asymptomatic atherosclerosis progression
Belcaro G. 1, Dugall M. 1, Hosoi M. 1, Ippolito E. 2, Cesarone M. R. 3, Luzzi R. 1, Cornelli U. 1, Ledda A. 1
1 Irvine3 Circulation Sciences, Department of Biomedical Sciences, G. D’Annunzio University, Pescara, Italy;
2 Vascular Surgery, University of Milan, Milan, Italy
Aim: The aim of the study was to evaluate the effect of the nutritional supplements Pycnogenol and TECA (total triterpenic fraction of Centella Asiatica) on atherosclerosis progression in low-risk asymptomatic subjects with carotid or femoral non-stenosing plaques.
Methods: This was an observational pilot substudy of the San Valentino epidemiological cardiovascular study. The study included 1363 subjects aged 45-60 without any conventional risk factors who had non stenosing atherosclerotic plaques (<50%) in at least one carotid or common femoral bifurcation, allocated into 6 groups: Group 1 (CONTROLS): management was based on education, exercise, diet and lifestyle changes. This same management plan was used in all groups; Group 2 Pycnogenol 50 mg/day; Group 3 Pycnogenol 100 mg/day; Group 4 Aspirin 100 mg/day or Ticlopidine 250 mg/day if intolerant to aspirin; Group 5 Aspirin 100 mg/day and Pycnogenol 100 mg/day; Group 6 Pycnogenol 100 mg/day plus TECA (total triterpenic fraction of Centella Asiatica) 100 mg/day. There was a six monthly follow-up up to 30 months. Plaque progression was assessed using the ultrasonic arterial score based on the arterial wall morphology and the number of plaques that progressed from the non-stenotic to the stenotic group. A secondary endpoint was to evaluate the changes in oxidative stress at baseline and at 30 months.
Results: The ultrasonic score increased significantly in groups 1, 2 and 4 but not in groups 3, 5 and 6 suggesting a beneficial effect of Pycnogenol 100 mg. The percentage of plaques that progressed from class IV to class V was 8.4% in group 2, 5.3% in group 3, 4% in group 5 and 1.1% in group 6 (P<0.0001) compared with 16.6% in group 4 (aspirin) and 21.3% in the control group suggesting a beneficial effect of Pycnogenol. The lowest rate of progression was in group 6 (Pycnogenol plus TECA). At 30 months, the oxidative stress in all the Pycnogenol groups was less than in the control group. The oxidative stress was lower in the Pycnogenol 100 mg group than the Pycnogenol 50 mg group (P<0.0001). In the combined group of Pycnogenol and TECA the oxidative stress was less than the Pycnogenol alone (P<0.001).
Conclusion: Pycnogenol and the combination of Pycnogenol+TECA appear to reduce the progression of subclinical arterial lesions in low-risk asymptomatic subjects. The reduction in plaque progression was associated with a reduction in oxidative stress. The results justify a large randomized controlled study to demonstrate the efficacy of the combined Pycnogenol and TECA prophylactic therapy in subclinical atherosclerosis.
Source : International Angiology
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Cranberry Juice Consumption May Reduce Arterial Stiffness in Overweight Men
Ruel G, Lapointe A, Pomerleau S, et al. Evidence that cranberry juice may improve augmentation index in overweight men. Nutr Res. 2013;33(1):41-49.
Endothelial dysfunction, the impairment of the normal functions of the inner lining of the blood vessels, is associated with cardiovascular disease (CVD) risk factors that can lead to arterial stiffness. The augmentation index (AIx) is an index of arterial stiffness measured by peripheral pulse wave analysis. Healthy nutritional habits, including increasing the consumption of fruits and vegetables and reducing dietary fat intake, are important in helping to prevent and treat CVD through improved lipoprotein-lipid and inflammatory profiles and endothelial function. The cardioprotective potential of fruits and vegetables is due to their high content of polyphenolic compounds such as flavonoids, which play a beneficial role in protecting against inflammation and oxidative stress. Cranberries (Vaccinium macrocarpon) are rich in polyphenols such as phenolic acids, flavonols, anthocyanins, and proanthocyanidins. The authors conducted a short-term, placebo-controlled, double-blind, crossover study at Université Laval in Quebec, Canada to examine the effect of consuming a low-calorie cranberry juice cocktail (CJC) on the AIx and cardiometabolic profile of overweight men.
The authors recruited 35 sedentary, otherwise healthy, overweight men (mean age = 45 ± 10 years) with a body mass index (BMI) of ≥ 25 kg/m2 and a waist circumference of ≥ 90 cm (35.4 inches). The men were nonsmokers and were not taking medications that affected lipid or insulin metabolism or blood pressure.
After a 4-week run-in period during which the subjects drank 500 mL of water daily to get used to that amount of liquid in their usual diet, they were randomly assigned to drink 500 mL daily of either a low-calorie CJC (27% juice) or placebo juice (PJ) for 4 weeks (2 boxes of 125 mL of juice in the morning and 2 in the evening). Then, after a 4-week washout period, the subjects began the other treatment for another 4 weeks.
The CJC and PJ (Ocean Spray Cranberries, Inc.; Lakeville-Middleboro, Massachusetts) had a similar taste, color, texture, and vitamin C content, but no cranberries were in the PJ. Each daily serving of the CJC contained 500 mg of total polyphenols, 20.8 mg of anthocyanins, and 21.84 g of carbohydrates.
At baseline and after week 4, body weight, height, waist and hip circumferences, and blood pressure were measured; BMI and waist-to-hip ratio values were calculated; and fasting blood samples were drawn. The subjects also completed a food frequency questionnaire at those 2 visits.
At baseline and at 4 weeks, the resting AIx was measured by applanation tonometry, during which peripheral artery waveforms were recorded on the subjects' radial artery. Waveforms were recorded again at 5, 10, 15, and 20 minutes after the subjects inhaled 400 μg of salbutamol, which elicits the synthesis of nitric oxide (NO) and a vascular response used as a proxy measure of endothelium-dependent vasodilation. The same technique was used to measure arterial stiffness during endothelium-independent radial artery vasodilation at 3, 5, 10, 15, 20, and 30 minutes following sublingual administration of 400 μg of glyceryl trinitrate (GTN), an NO donor used to treat angina and heart failure. The cardiometabolic profile, which assesses risks associated with type 2 diabetes mellitus and CVD, was determined for each subject before and after each phase of the study.
The subjects were separated into groups made up of those with metabolic syndrome (MetS+) (n = 13) and those without metabolic syndrome (MetS-) (n = 22), using the criteria for metabolic syndrome as defined by the National Cholesterol Education Program.
At baseline, although at the high end for total fat intake and the low end for carbohydrate intake, the daily energy and nutrient intakes of the subjects fell within the nutritional recommendations for Canadian adults. The MetS+ subjects had a higher BMI, higher circulating triglycerides (TG), and lower high-density lipoprotein cholesterol (HDL-C) levels compared with the MetS- subjects.
The authors report that the salbutamol reduced the AIx by 10.8% ± 6.4% compared with resting values (P < 0.0001). GTN further decreased the values by 2.1% ± 6.0% compared with salbutamol (P < 0.05). However, these changes in the AIx responses to salbutamol and GTN did not significantly differ between subjects who consumed the CJC or PJ.
Although no significant difference was noted in the AIx changes between the subjects who consumed the CJC or PJ, a statistically significant within-group decrease was noted in the AIx (P < 0.05 compared with baseline) in subjects who consumed the CJC.
No significant differences were noted in other cardiometabolic variables between those subjects drinking the CJC or PJ.
Comparing the AIx values in the MetS+ and MetS- subjects, the authors report no significant differences in the responses to salbutamol and GTN after supplementation; however, they noted a significant within-group decrease in the resting AIx values in MetS- subjects who drank CJC (P < 0.05 compared with baseline). In those same subjects, significant increases in the AIx responses to salbutamol and GTN were observed (P < 0.05 compared with baseline). Although these results may seem contradictory, say the authors, earlier studies have shown that, "Vascular tone is positively correlated with flow-mediated dilation in healthy individuals, and thus, a more relaxed (and possibly wider) artery at rest has a lower endothelium-dependent vasodilation response."
The authors previously reported that CJC supplementation was associated with reductions in circulating oxidized low-density lipoprotein (OxLDL) and adhesion molecule concentrations (inflammation and oxidative stress markers) in men.1,2 This was not supported, however, in the present study, where no significant changes in those markers were reported after the CJC supplementation. Although the differences in the design of the studies may explain the discrepancies, say the authors, the lack of effect of the CJC on plasma OxLDL and adhesion molecule levels in the current study agrees with previous reports showing that CJC consumption for 2 weeks had no effect on oxidative stress markers3 and that supplementing men and women with a 54% CJC for 4 weeks did not reduce cell adhesion molecule concentrations.4
These authors found that although CJC consumption did reduce the resting AIx in overweight men, the decrease was not significantly different from those drinking the PJ. The significant within-group decrease in the AIx following the CJC consumption, however, warrants further investigation.
1Ruel G, Pomerleau S, Couture P, Lamarche B, Couillard C. Changes in plasma antioxidant capacity and oxidized low-density lipoprotein levels in men after short-term cranberry juice consumption. Metabolism. 2005;54(7):856-861.
2Ruel G, Pomerleau S, Couture P, Lemieux S, Lamarche B, Couillard C. Low-calorie cranberry juice supplementation reduces plasma oxidized LDL and cell adhesion molecule concentrations in men. Br J Nutr. 2008;99(2):352-359.
3Duthie SJ, Jenkinson AM, Crozier A, et al. The effects of cranberry juice consumption on antioxidant status and biomarkers relating to heart disease and cancer in healthy human volunteers. Eur J Nutr. 2006;45(2):113-122.
4Dohadwala MM, Holbrook M, Hamburg NM, et al. Effects of cranberry juice consumption on vascular function in patients with coronary artery disease. Am J Clin Nutr. 2011;93(5):934-940.
Source : American Botanical Council
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Dietary oats and modulation of atherogenic pathways
- Kristina E. Andersson*,
- Per Hellstrand
Consumption of oats has long been known to lower plasma total and low-density lipoprotein (LDL) cholesterol levels, an effect usually attributed to the soluble fibers β-glucans. On the basis of this cholesterol-lowering effect, oats are ascribed cardiovascular health-promoting properties. However, besides cholesterol levels, effects of oats on parameters relating to atherosclerosis development have not been extensively investigated. Since oxidation of lipoproteins and inflammation are characteristics of atherosclerosis in addition to lipid accumulation in the vessel wall, micronutrients in oats (phytochemicals) with antioxidative and anti-inflammatory properties may contribute to an atheroprotective action. Here, we summarize evidence on antiatherogenic properties of oats obtained from in vitro assays, animal experiments, and human studies. Possible effects involving anti-inflammatory and antioxidative actions, as well as preservation of endothelial function, are considered in addition to those related to reduction of plasma cholesterol. Since results of in vitro assays with isolated oat components are difficult to compare with effects of whole oats in humans and experimental animals, more observational studies with isolated oat components or fractions of oats are warranted. Also, there is a lack of epidemiological studies focusing on effects of oat intake on the cardiovascular disease panorama.
....The action of various oat components on the atherogenic pathways reviewed here suggest that several different oat components besides β-glucans may confer an atheroprotective effect of possible significance for cardiovascular health.
Source : Molecular Nutrition and Food Research
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Dietary Antioxidants: From Micronutrients and Phytochemicals to Enzymes – Preventive Effects on Early Atherosclerosis and Obesity
Sylvie Gaillet1, Dominique Lacan2 and Jean-Max Rouanet1
1UMR 204 NUTRIPASS, Université Montpellier
2, Montpellier, 2BIONOV S.A.R.L., Montpellier, France
Development of atherosclerosis is thought to be closely dependent upon increased oxidative stress, that is, an imbalance between reactive oxygen species (ROS). Elsewhere, high-fat diets and sedentary lifestyles are important risk factors for obesity, which is a key feature of metabolic syndrome and which greatly predisposes individuals to liver diseases, cardiovascular disease (CVD), type 2 diabetes, dyslipidemia, hypertension, and numerous cancers and is associated with markedly diminished life expectancy. Today, due to oxidative stress, the postulated involvement of lipid peroxidation in atherogenesis and obesity invoked intensive interest in the use of antioxidant nutritional supplements. Epidemiological evidence suggests that intake of some vitamins, minerals, and other food constituents may help to protect against heart disease, obesity, cancer and the aging process and that antioxidants may have a protective effect, in either preventing these diseases or lessening the severity of the diseases upon their onset
.....Dietary antioxidants can play a key role in the regulation of the oxidant status and it seems essential to develop and utilise natural antioxidants so that they can retard the progress of many chronic diseases. The consumption of antioxidant rich fruits and vegetables that generally supplies minerals, vitamins, fibers, phytochemicals such as phenolics but also provides antioxidant enzymes is therefore advised
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Therapeutic effects of water soluble danshen extracts on atherosclerosis.
Cho YH, Ku CR, Hong ZY, Heo JH, Kim EH, Choi DH, Kim D, Kim AJ, Lee CS, Jung M, Lee HC, Seo M, Lee EJ.
Severance Hospital Integrative Research Institute for Cerebral & Cardiovascular Diseases, Severance Hospital, Seoul 120-752, Republic of Korea.
Danshen is a traditional Chinese medicine with many beneficial effects on cardiovascular diseases. The aim of this study was to evaluate the mechanisms responsible for the antiatherogenic effect of water soluble Danshen extracts (DEs). Rat vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) were treated with DE. To evaluate the effects of DE in vivo, carotid balloon injury and tail vein thrombosis were induced in Sprague-Dawley (SD) rats and iliac artery stent was induced in New Zealand white rabbits. The inhibitory action of DE on platelet aggregation was confirmed with an impedance aggregometer. DE inhibited the production of reactive oxygen species, and the migration and proliferation of platelet-derived growth factor-BB stimulated VSMCs. Furthermore, DE prevented inflammation and apoptosis in HUVECs. Both effects of DE were reconfirmed in both rat models. DE treatment attenuated platelet aggregation in both in vivo and ex vivo conditions. Pretreatment with DE prevented tail vein thrombosis, which is normally induced by κ-carrageenan injection. Lastly, DE-treated rabbits showed decreased in-stent restenosis of stented iliac arteries. These results suggest that water soluble DE modulates key atherogenic events in VSMCs, endothelial cells, and platelets in both in vitro and in vivo conditions.
Source : Evid Based Complement Alternat Med. 2013; 2013: 623639. Published online 2013 January 16. doi: 10.1155/2013/623639
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Anti-atherosclerotic function of Astragali Radix extract: downregulation of adhesion molecules in vitro and in vivo
Yang You, Yan Duan, Shao-wei Liu, Xiao-lin Zhang, Xiu-li Zhang, Jia-tao Feng, Cheng-hui Yan, Ya-ling Han
1 Department of Cardiology, Cardiovascular Research Institute, Shenyang Northern Hospital, Shenyang, China
2 The Affiliated Hospital of Liaoning University of TCM, Shenyang, China
3 Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
Atherosclerosis is considered to be a chronic inflammatory disease. Astragali Radix extract (ARE) is one of the major active ingredients extracted from the root of Astragalus membranaceus Bge. Although ARE has an anti-inflammatory function, its antiatherosclerotic effects and mechanisms have not yet been elucidated.
Murine endothelial SVEC4-10 cells were pretreated with different doses of ARE at different times prior to induction with tumor necrosis factor (TNF)-α. Cell adhesion assays were performed using THP-1 cells and assessed by enzyme-linked immunosorbent assay, western
blotting and immunofluorescence analyses to detect the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), phosphorylated inhibitor of κB (p-iκB) and nuclear factor (NF)-κB. We also examined the effect of ARE on
atherosclerosis in the aortic endothelium of apolipoprotein E-deficient (apoE−/−) mice.
TNF-α strongly increased the expression of VCAM-1 and ICAM-1 accompanied by increased expression of p-iκB and NF-κB proteins. However, the expression levels of VCAM-1 and ICAM-1 were reduced by ARE in dose- and time-dependent manners, with the strongest effect at a dose of 120 μg/ml incubated for 4 h. This was accompanied by significantly decreased expression of p-iκB and inhibited activation of NF-κB.
Immunofluorescence analysis also revealed that oral administration of ARE resulted in downregulation of adhesion molecules and decreased expression of macrophages in the aortic endothelium of apoE−/− mice. ARE could suppress the inflammatory reaction and inhibit the
progression of atherosclerotic lesions in apoE−/− mice.
This study demonstrated that ARE might be an effective anti-inflammatory agent for the treatment of atherosclerosis, possibly acting via the decreased expression of adhesion molecules.
Source : BMC Complementary and Alternative Medicine 2012, 12:54 doi:10.1186/1472-6882-12-54
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