Circulating odd-chain saturated fatty acids were associated with arteriosclerosis among patients with diabetes, dyslipidemia, or hypertension in Sri Lanka but not Japan.

The differences in the morbidity and mortality of cardiovascular diseases between Sri Lankan and Japanese populations might be explained by the differences in their diet, especially fat. To test the hypothesis that the fatty acid (FA) compositions differ between Sri Lankan and Japanese populations and that high concentrations of n-3 polyunsaturated FAs and linoleic acid are associated with a low level of arteriosclerosis, the authors compared the circulating FA compositions between Sri Lankan and Japanese populations and examined the association of the circulating FA composition with arterial stiffness in each population. The study participants were patients with diabetes, dyslipidemia, or hypertension in Sri Lanka (n = 100) or Japan (n = 236). Serum FA compositions were measured by gas chromatography. Arterial stiffness was measured using the cardio-ankle vascular index (CAVI). Analysis of covariance was used to compare the FA compositions between the populations. Multiple regression was used to assess the association between each FA and CAVI levels. The concentrations of myristic, γ-linolenic, dihomo-γ-linolenic, and arachidonic acids were higher in the Sri Lankan patients than in the Japanese patients. In contrast, the concentrations of linoleic, α-linolenic, and eicosapentaenoic acids were higher in the Japanese patients than in the Sri Lankan patients. Although no associations of n-3 polyunsaturated FAs and linoleic acid with CAVI were observed in both patient populations, odd-chain saturated FAs (pentadecanoic and heptadecanoic acids) were significantly inversely associated with CAVI levels in the Sri Lankan (P for trend = .03) but not the Japanese patients. The odd-chain saturated FAs might be inversely associated with atherosclerosis in this Sri Lankan population.

Anthocyanin Rich-Black Soybean Testa Improved Visceral Fat and Plasma Lipid Profiles in Overweight/Obese Korean Adults: A Randomized Controlled Trial.

Anthocyanin-rich black soybeans have been used in traditional East Asian medicine to cure diseases related to oxidative stress and carcinogens, but not obesity. Our objective was to investigate the effects of anthocyanin-rich black soybean testa extracts (BBT), Glycine max (Chongja No. 3), on obesity. In total, 63 participants defined as overweight or obese by their body mass index (BMI >23) or waist circumference (WC >90 cm for males, >85 cm for females) were sorted into two groups: 32 receiving the trial medication (BBT, 2.5 g/d) and 31 receiving the placebo (starch, 2.5 g/d). Participants completed an 8-week, randomized, double-blinded, and placebo-controlled clinical trial. There were no significant differences between the two groups at the beginning of the trial, and both required the same safety assessments. Significant decreases in abdominal fat, described according to WC and hip circumference, and lipid profiles such as triacylglycerols (TG), low density lipoprotein cholesterol (LDLc), and non-high density lipoprotein cholesterol (non-HDLc) were observed in the BBT group at the conclusion of the clinical trial. The indicators for arteriosclerosis such as total cholesterol (TC)/HDLc and LDLc/HDLc were significantly decreased in the BBT group, but had not changed in the placebo group. With no difference between the two groups in energy-adjusted dietary intakes and physical activity, BBT was shown to strongly improve plasma lipid profiles, related to the reduction of WC (an indicator of abdominal fat) as long as high dietary fiber and low cholesterol diets were maintained. In conclusion, BBT can potentially be developed as a functional food for preventing abdominal obesity with high fiber and low cholesterol diets.

Serum ß-cryptoxanthin and ß-carotene derived from Satsuma mandarin and brachial-ankle pulse wave velocity: The Mikkabi cohort study.

BACKGROUND AND AIMS: Findings of observational studies suggest cardioprotective effects of antioxidant vitamins and carotenoids. However, recent meta-analyses failed to show the beneficial effects of supplemental intake of antioxidants on cardiovascular disease (CVD). We aimed to assess the association between CVD risk and ß-cryptoxanthin in Japan, where Satsuma mandarin, a major source of ß-cryptoxanthin, is widely consumed. METHODS AND RESULTS: This was part of the Mikkabi cohort study. Surveys were conducted at baseline, in 2003 and 2005, and on follow-up in 2006, 2009, and 2013. We examined brachial-ankle pulse wave velocity (baPWV) with a high cut-off value set at 18.3 m s(-1). Hazard ratios (HR) and 95% confidence intervals for high baPWV were estimated using a Cox proportional hazards model with adjustment for potential confounders. A total of 635 participants with baPWV of less than 18.3 m s(-1) at baseline were included in the analysis. During the follow-up period of 57,921 person-months, 99 subjects developed high baPWV. After multivariate adjustment, the HR for high baPWV in the highest tertile compared with the lowest tertile was significantly low for ß-cryptoxanthin, ß-carotene, and total carotenoids. Serum concentrations of ß-cryptoxanthin and ß-carotene were higher in people who ate Satsuma mandarin frequently. Compared with <1/d intake of Satsuma mandarin, 3-4/d was associated with a low risk of high PWV. CONCLUSION: This study indicated that ß-cryptoxanthin and ß-carotene derived from Satsuma mandarin are candidate micronutrients for preventing arteriosclerosis development. Further longitudinal and interventional studies will be required to validate the effect on CVD.

A study on the effect of resveratrol on lipid metabolism in hyperlipidemic mice.

BACKGROUND: The content of resveratrol is relatively high in Polygonum cuspidatum Sieb. et Zucc., and the resveratrol has the effect of blood vessel dilating, microcirculation improving, platelet aggregation inhibiting and anti-cancer. The objective of this paper was to study the effect of resveratrol on lipid metabolism in hyperlipidemia mice. MATERIALS AND METHODS: Through the establishment of an experimental mouse model of hyperlipidemia, the effect of resveratrol on change in total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) levels in mouse serum were determined. RESULTS: Resveratrol group can apparently reduce TC, TG, LDL-c and AI of hyperlipidemic mice in a dose effect manner. CONCLUSION: We concluded that resveratrol can effectively reduce blood lipid levels of hyperlipidemic mice.

Homocysteine lowering interventions for peripheral arterial disease and bypass grafts.

BACKGROUND: Elevated plasma levels of the amino acid homocysteine (hyperhomocysteinaemia) are associated with narrowing or blocking of the arteries (atherosclerosis). Treatment to lower homocysteine levels has been shown to be both effective and cheap in healthy volunteers. However, the impact of reducing homocysteine levels on the progression of atherosclerosis and patency of the vessels after treatment for atherosclerosis is still unknown and forms the basis for this review. This is the second update of a review first published in 2002. OBJECTIVES: To assess the effects of plasma homocysteine lowering therapy on the clinical progression of disease in people with peripheral arterial disease (PAD) and hyperhomocysteinaemia including, as a subset, those who have undergone surgical or radiological intervention. SEARCH METHODS: For this update, the Cochrane Peripheral Vascular Disease Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched January 2013) and CENTRAL (2012, Issue 12). Trial databases were searched by the TSC (January 2013) for details of ongoing and unpublished studies. We also searched the reference lists of relevant articles. SELECTION CRITERIA: Randomised trials in which participants with PAD and hyperhomocysteinaemia were allocated to either homocysteine lowering therapy or no treatment, including participants before and after surgical or radiological interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted the data. Information on adverse events was collected from the trials. MAIN RESULTS: Two randomised trials with a total of 161 participants were included in this review. The studies did not report on mortality and rate of limb loss. One randomised trial with a total of 133 participants showed that there was a significant improvement in ankle brachial index (ABI) in participants who received folic acid compared with placebo (mean difference (MD) 0.07, 95% confidence interval (CI) 0.04 to 0.11, P < 0.001) and in participants who received 5-methyltetrahydrofolate (5-MTHF) versus placebo (MD 0.05, 95% CI 0.01 to 0.10, P = 0.009). A second trial with a total of 18 participants showed that there was no difference (P non-significant) in ABI in participants who received a multivitamin B supplement (mean ± SEM: 0.7 ± 01) compared with placebo (mean ± SEM: 0.8 ± 0.1). No major events were reported. AUTHORS' CONCLUSIONS: Currently, no recommendation can be made regarding the value of treatment of hyperhomocysteinaemia in peripheral arterial disease. Further, well constructed trials are urgently required.

Relationship between magnesium and clinical biomarkers on inhibition of vascular calcification.

BACKGROUND: Arteriosclerosis and cardiovascular disease are strongly associated with vascular calcification. Hyperphosphatemia is an essential risk factor for increased vascular calcification. End-stage renal disease (ESRD) patients could serve as an in vivo model for accelerated calcification. This study focuses on the most likely protective effects of magnesium ion (Mg(2+)) on phosphate-induced vascular calcification ex vivo/in vitro. Furthermore, plasma Mg(2+) concentrations of ESRD and healthy controls were investigated for association with surrogate parameters of vascular calcification in vivo. METHODS: Aortic segments of male Wistar-Kyoto rats were incubated and the phosphate concentration of the medium was elevated. The aortic segments were incubated in the absence and presence of MgCl(2); tissue calcification was quantified by different methods. Serum Mg(2+) concentrations of patients with chronic kidney disease (CKD stage 5; ESRD) and patients without CKD (controls) were associated with carotid intima media thickness (IMT) and aortic pulse wave velocity (PWV) as surrogate parameter for arteriosclerosis and arterial stiffening. RESULTS: Incubation of aortic segments in the presence of ß-glycerophosphate and NaH(2)PO(4) caused an increased tissue Ca(2+) deposition compared to control conditions. This increased amount of Ca(2+) in the aortic rings was significantly decreased in the presence of Mg(2+). In CKD patients, but not in controls, magnesium serum concentration was associated with the IMT of the carotid arteries. In addition, CKD patients with higher magnesium serum concentration had a significantly lower PWV. DISCUSSION AND CONCLUSION: Elevated phosphate concentrations in the culture media induce ex vivo/in vitro medial calcification in intact rat aortic rings in the presence of alkaline phosphatase. Mg(2+) ions reduced ex vivo/in vitro vascular calcification despite increased phosphate concentration. This hypothesis is additionally based on the fact that CKD patients with high Mg(2) serum levels had significantly lower IMT and PWV values, which may result in a lower risk for cardiovascular events and mortality in these patients. Therefore, Mg(2+) supplementation may be an option for treatment and prevention of vascular calcification resulting in a reduction of cardiovascular events in CKD patients.

[Effect of conjugated linoleic acid (CLA) on human lipid profile]. / Efecto del ácido linoleico conjugado (CLA) sobre el perfil lipídico en humanos.

The term conjugated linoleic acid (CLA) concerns a group of isomers of linoleic acid, which are characterized by having conjugated double bonds in several positions and conformations. CLA is found naturally in some foods, but since CLA was first held to cause beneficial effects on various health-related issues, many investigations have been conducted to elucidate the effects of dietary supplementation with CLA. The effects of CLA on lipid profiles on animals have been extensively studied, and there is sound evidence of its benefits in blood metabolic markers. However, clinical trials in humans have provided ambiguous results. The aim of this review was to gather up-to-date available data about the effects of CLA on human lipid profile. Although most studies did not show any significant effect in none of the studied variables, some trials reported both beneficial and detrimental effects on total cholesterol, LDL-c, HDL-c, atherogenic index, triglycerides and lipoprotein(a). This discrepancy could be due to differences in dosage, isomer composition, duration of the study, placebo and participating subjects, among others. However, studies with a duration of two weeks, carried out using a mix of equal amounts of the two main CLA isomers (9-cis, 11-trans and 10-trans, 12-cis) and with doses of 3 to 4 grams per day, seem to offer the most beneficial results.

Effects of Garcinia atroviridis on serum profiles and atherosclerotic lesions in the aorta of guinea pigs fed a high cholesterol diet.

INTRODUCTION: The fruit extract of Garcinia atroviridis (G. atroviridis) contains hydroxycitric acid and flavonoids, which have been reported to have a hypolipidaemic property. This extract with solvent methanol was used to investigate its effects on serum lipid profiles of guinea pigs fed a high cholesterol diet. METHODS: 24 male Dunkin Hartley guinea pigs were randomly divided into four groups. The first group served as controls and was fed with commercial rabbit chow. The second group was given only G. atroviridis by oral gavage (50 mg/body weight). The third group was fed a one percent cholesterol diet in food pellets in order to induce atherosclerosis. The fourth group was administered G. atroviridis with cholesterol. All the treatments were given daily for eight weeks, after which the animals were sacrificed, and the blood and aorta were taken for biochemical analysis and histological studies. RESULTS: The supplementation of G. atroviridis with a cholesterol diet decreased the level of lipid profile in the serum. Histological studies showed a reduction in fat deposition in the aorta of high cholesterol diet animals given G. atroviridis as compared to the high cholesterol diet group. CONCLUSION: This study has shown that dietary intake of G. atroviridis has a tendency to decrease lipid composition levels in the serum and reduce fat deposition in the aorta of high cholesterol diet animals.

Effect of low dose antioxidant vitamin and trace element supplementation on the urinary concentrations of thromboxane and prostacyclin metabolites.

OBJECTIVE: This trial evaluated the effect of antioxidant supplementation on the urinary excretion of 11-dehydro TXB(2)/2,3 dinor 6 keto PGF(1alpha) ratio, a marker of the pathogenesis of thrombosis and arteriosclerosis. METHODS: This study was a randomised, double-blind, placebo-controlled trial involving 186 presumably healthy volunteers. One hundred received a multi-antioxidant supplementation and 86 a placebo for two years. Blood zinc, selenium, beta-carotene, vitamin C and E and urinary excretion of 11-dehydro TXB(2) and 2,3 dinor 6 keto PGF(1alpha) were measured. RESULTS: Baseline subject characteristics did not differ between the two groups. Blood zinc, selenium, and beta-carotene concentrations significantly increased between baseline and two years in the multi-antioxidant supplementation group supporting subject compliance (p < 0.05). At two years, the median urinary 11-dehydro TXB(2)/2,3 dinor 6 keto PGF(1alpha) ratio was significantly lower in the multi-antioxidant supplementation group (3.4 versus 2.78, p = 0.015). Serum selenium concentration was the only antioxidant studied that was significantly related to the urinary 11-dehydro TXB(2)/2,3 dinor 6 keto PGF(1alpha) ratio. CONCLUSIONS: These results support the hypothesis that a low-dose multi-antioxidant supplementation may contributes to a reduction in platelet activation which is beneficial for cardiovascular function.

[Experimental study of anti-atherosclerosis potency by lycium seed oil and its possible mechanism].

OBJECTIVE: To study the effect of anti-atherosclerosis of Lycium Seed Oil (Lso) and its possible mechanism. METHODS: The rabbit atherosclerosis model was established by high fat diet, and the TC, TG, LDL-C, HDL-C levels in plasma were examined dynamically. The SOD, GSH-PX, T-AOC activities and the MDA levels in serum were monitored after 8 week's high fat diet. Aorta samples were observed for atherosclerotic extent, and NF-kappaB, TNF-alpha were assessed by immuno-histochemical method. The lovastatin was set up as a positive control. RESULTS: contents of HDL-C obviously increased in Plasma of low and high dosage groups and TC, TG, LDL-C levels significantly decreased compared with control group. The SOD, GSH-PX, T-AOC activities up-regulated while the NF-kappaB, MDA and NF-alpha levels decreased in Lycium Seed Oil groups compared with control group. Aortic atherosclerotic extent and area in low dosage and high dosage LSO groups were absolutely smaller than that in high fat diet group. The anti-atherosclerosis potency of Lycium Seed Oil was similar with that of lovastatin. CONCLUSION: Lycium Seed Oil has potent anti-atherosclerosis effects and its anti-atherosclerosis potency was similar with The lovastatin. The possible mechanism involve the decreasing of plasma lipids, anti-peroxidation, inhibiting the activation of NF-kappaB and down-regulating the inflammation cytokines of TNF-alpha.

Ginkgo biloba (EGb 761) in arteriosclerosis prophylaxis.

The prevention or deceleration of atherogenesis is one of the most significant anti-aging objectives since this is a matter of avoidance of myocardial infarction and stroke. To approach this prophylactic aim, phytochemical nutrition counteracting peroxidation of blood lipids based on their scavenger qualities for reactive oxygen species (ROS) can possibly serve. For example, oxidized LDL particles are highly atherogenic. Against this background, we investigated in a pilot study the effect of Ginkgo biloba (EGb 761: Rökan novo), the free oxygen radical scavenging properties of which are well-documented, on the atherosclerotic nanoplaque formation in cardiovascular high-risk patients. In eight patients who had undergone an aortocoronary bypass operation, the reduction of atherosclerotic nanoplaque formation amounted to 11.9 +/- 2.5% (p < 0.0078) and of nanoplaque size to 24.4 +/- 8.1% (p < 0.0234), respectively, after a 2-month therapy with Ginkgo biloba extract (EGb 761, 2 x 120 mg daily, Rökan novo, Spitzner Arzneimittel, Ettlingen, Germany). Additionally, superoxide dismutase (SOD) activity was upregulated by 15.7 +/- 7.0% (p < 0.0391), the quotient oxLDL/LDL lowered by 17.0 +/- 5.5% (p < 0.0234) and lipoprotein(a) concentration decreased by 23.4 +/- 7.9% (p < 0.0234) in the patients' blood after the 2-month medication regimen. The concentration of the vasodilating substances cAMP and cGMP was augmented by 37.5 +/- 9.1% (p < 0.0078) and 27.7 +/- 8.3% (p < 0.0156), respectively. A multimodal regression analysis reveals a basis for a mechanistic explanation of nanoplaque reduction under ginkgo treatment. The atherosclerosis inhibiting effect is due to an upregulation in the body's own radical scavenging enzymes and an attenuation of the risk factors oxLDL/LDL and Lp(a). Furthermore, the significant increase in the vasodilator cAMP and cGMP concentration powerfully supports the maintenance of an open bypass.

Vaccines for the prevention of cardiovascular disease.

Atherosclerosis, especially coronary heart disease (CHD), remains a most significant global public health problem. Highly effective LDL-lowering therapies have gained widespread adoption in the United States and throughout the developed world, but therapeutic options for raising low HDL, a key independent risk factor for CHD, remain limited. We are developing a vaccine approach to raising HDL, by inducing an immune response to endogenous cholesteryl ester transfer protein (CETP), and have demonstrated proof of principle in preclinical and clinical models. This vaccine approach may offer the opportunity to address low HDL with a cost-effective semi-annual injection.

Chunghyul-dan (Qingxie-dan) improves arterial stiffness in patients with increased baPWV.

Arterial stiffness is an important, independent determinant of cardiovascular risk. Pulse wave velocity (PWV) has been used as a valuable index of arterial stiffness and as a surrogate marker for atherosclerosis. Chunghyul-dan (CHD) has anti-hyperlipidemic activity, anti-inflammatory activity and anti-atherogenic effects. To determine its clinical effect on increased arterial stiffness, we examined whether CHD improves arterial stiffness in patients with increased brachial-ankle PWV (baPWV). Thirty-five subjects with increased baPWV (> 1400 cm/sec) were recruited and randomized to a treatment group (20 subjects) or a control group (15 subjects). The treatment group was administered CHD at a dose of 600 mg three times a day for 8 weeks, and the control group received no medication (observation only). baPWV was assessed using a pulse pressure analyzer at baseline and after 8 weeks. Blood pressure and serum lipid profile were monitored in the treatment group. Our results indicate that baPWV was lowered significantly in the treatment group after 8 weeks of medication (p < 0.05), but not in the control group. Moreover, there were no significant changes in blood pressure and serum lipids profile except triglyceride level suggesting that the effect is largely independent of CHD's lipid-lowering effect or a blood pressure change. In conclusion, CHD appears to improve arterial stiffness in patients with increased PWV.

Asymmetric dimethylarginine (ADMA): a novel risk marker in cardiovascular medicine and beyond.

There is abundant evidence that the endothelium plays a crucial role in the maintenance of vascular tone and structure. One of the major endothelium-derived vasoactive mediators is nitric oxide (NO), an endogenous messenger molecule formed in healthy vascular endothelium from the amino acid precursor L-arginine. Endothelial dysfunction is caused by various cardiovascular risk factors, metabolic diseases, and systemic or local inflammation. One mechanism that explains the occurrence of endothelial dysfunction is the presence of elevated blood levels of asymmetric dimethylarginine (ADMA)--an L-arginine analogue that inhibits NO formation and thereby can impair vascular function. Supplementation with L-arginine has been shown to restore vascular function and to improve the clinical symptoms of various diseases associated with vascular dysfunction.

Association between nutrient intake and peripheral artery disease: results from the InCHIANTI study.

BACKGROUND: Little is known about the relationship between dietary patterns and peripheral arterial disease (PAD). Our aim was to estimate the association between nutrient intake and diagnosis of PAD. METHODS AND RESULTS: We assessed the nutrient intake of 1251 home-dwelling subjects enrolled in the InCHIANTI study, mean age 68 years (S.D.: 15). We explored the relationship between nutrient intake, obtained through the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire, and PAD, defined as an ankle-brachial index (ABI)<0.90. After adjustment for potential confounders, we found a reduction of the risk of having an ABI<0.90 associated with vegetable lipid intake>or=34.4 g/day (OR: 0.39; 95% CI: 0.16-0.97), Vitamin E intake>or=7.726 mg/day (OR: 0.37; 95% CI 0.16-0.84) and higher serum HDL cholesterol concentration (OR: 0.76; 95% CI: 0.63-0.92 for 10mg/dl increase). Age (OR: 1.11; 95% CI 1.07-1.14 for 1 year increase), smoking (OR: 1.03; 95% CI: 1.01-1.04 for 10 packs/year increase) and pulse pressure (OR: 1.11; 95% CI: 1.03-1.19 for 5 mmHg increase) were associated with an increased risk of PAD. CONCLUSIONS: A higher intake of vegetable lipids, Vitamin E and higher concentrations of serum HDL cholesterol characterize subjects free from PAD. Prospective studies are needed to verify whether this dietary pattern and/or interventions aimed at increasing HDL cholesterol exert some protective effect against PAD.

Plasma fibrinogen concentration in pediatric patients treated with an elimination diet based on soy proteins and casein hydrolyzate.

PURPOSE: Fibrinogen is one of the most discussed new risk factors of atherosclerosis. The aim of the study was to assess the relationship between fibrinogen concentration and classic risk markers of atherosclerosis in a group of children aged from 2 to 6 with or without a family history of circulatory system diseases (FHCAD) (American Academy of Pediatrics--AAP criteria). The study also considered the impact of allergies/food intolerance treatment with elimination diets on the concentration of atherosclerosis markers specially fibrinogen. INCLUSION CRITERIA: a) family history of early occurrence of circulatory system diseases (FHCAD+) according to AAP standards; b) the type and duration of elimination diet continued in infancy and early childhood. 134 of 388 children were included in the investigation. RESULTS: The analysis of data relating to the so-called classic biochemical risk factors of atherosclerosis (total cholesterol--TC, HDL, LDL, triglycerides, glucose) did not reveal any differences between the tested groups. It was found that in the FHCAD+ group the concentration of fibrinogen was statistically higher than in the group with a negative family history. It was discovered that the type of elimination diet had no effect on fibrinogen level in the FHCAD+ group. In the group of children with negative family history the concentration of fibrinogen was statistically lower in the group on casein hydrolysate than in children treated with soy formula. CONCLUSIONS: The initial interview in pediatrics should include information on the patient's family history of atherosclerosis. In case of a positive family history, fibrinogen, as one of atherosclerosis risk factors, should be monitored.

[Effect of Laminaria japonica polysaccharides on lowing serum lipid and anti-atherosclerosis in hyperlipemia quails].

OBJECTIVE: To study the effect of Laminaria Japonica Polysaccharides on lowing serum lipid and anti-atherosclerosis in quails. METHODS: The hyperlipemia atherosclerosis (As) models of quails were induced by high lipids. After administration with Laminaria Japonica Polysccharides for two weeks, the content of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) in serum and the ratio of HDL/TC were determined, index of liver was calculated, the extent of aortic atherosclerosis and the atherosclerotic lesion were observed. RESULTS: The concentration of TC, TG, LDL in serum and index of liver decreased remarkedly, the ratio of HLD/TC increased remarkably, the the extent of aortic atherosclerosis and the atherosclerotic lesion lightened obviously. CONCLUSION: Laminaria Japonica Polysaccharides can effectively decrease the serum lipid and prevent the formation of atherosclerosis.

Rapamycin attenuates atherosclerotic plaque progression in apolipoprotein E knockout mice: inhibitory effect on monocyte chemotaxis.

Rapamycin has been shown to reduce neointimal thickening in the setting of balloon angioplasty and chronic graft vessel disease. This study was designed to test the effect of oral rapamycin on atherosclerotic plaque progression and the possible mechanism involved. Apolipoprotein E (apoE) knockout mice were fed either a diet supplemented with cholesterol or with cholesterol and rapamycin. At 4 and 8 weeks, quantitative analyses of plaque area and macrophage numbers were determined. Plasma cholesterol, triglyceride, and whole-blood rapamycin levels were measured. Rapamycin could be detected in the blood of mice (117+/-7 pg/mL). In mice fed with rapamycin, atherosclerotic lesions covered 22% of the aortic arch as compared with 41% in cholesterol-fed mice. The macrophage count was significantly lower in the rapamycin-fed mice as compared with cholesterol-fed mice. Rapamycin, in a dose-dependent manner, inhibited monocyte chemotaxis elicited by stromal cell-derived factor-1. Lesions in the cholesterol-fed mice had complex atherosclerotic plaque with acellular core, cholesterol clefts, and an abundant collection of monocytes/macrophages. Lesions in the rapamycin-fed mice were mainly composed of monocytes/macrophages. Oral rapamycin is effective in slowing the progression of atherosclerosis. Along with its multitude actions, attenuation of monocyte chemotaxis may be one more way by which rapamycin attenuates plaque progression.

The high atherosclerotic risk among epileptics: the atheroprotective role of multivitamins.

Neurologists have little concern about the high atherosclerotic risk among epileptics. Recent evidences mount that chronic epilepsy and prolonged use of antiepileptic drugs (AEDs) are associated with multiple risk factors that are critically implicated in pathobiology and dysfunction of the vessel wall through complex molecular mechanisms that promote atherogenesis. This review is concerned with three metabolic alterations, which are attributed as major risk factors for atherosclerosis among epileptics: altered metabolism of a) homocysteine (Hcy), b) lipids and lipoproteins, and c) uric acid. Most conventional AEDs reduce folic acid levels, thereby raising Hcy levels. Hyperhomosysteinemia is recently believed to induce endothelial dysfunction and promote atherosclerosis through complex oxidative and excitatory neurotoxic molecular mechanisms. However, Hcy itself is a convulsing substance with increased seizure recurrence and intractability to antiepileptic medications. AEDs can disturb lipid metabolism with resultant hypercholestrolemia and dyslipidemia, common recognized risks for atherosclerosis. Altered uric acid metabolism is common among epileptics. Uric acid has been implicated in endothelial cell damage and decreased endothelial nitric oxide bioavailability. In the presence of atherosclerotic milieu, uric acid interacts with other substrate toxicities and increased reactive oxygen species, accelerating atherosclerosis. The above information forms the rationale for future routine screening and correction of such metabolic alterations in epileptics. A convincing argument now develops that routine polyvitamin supplementation (folic acid, vitamin B12, vitamin B6, vitamin C, vitamin E, and beta-carotene) becomes increasingly important for women and men receiving AEDs at all ages. The atheroprotective effect of multivitamins is through their antioxidant and anti-inflammatory effects together with their lipid and Hcy lowering effects.