Hypercholesterolemic Control Group Research Articles

Enhanced External Counterpulsation Attenuates Atherosclerosis Progression Through Modulation of Proinflammatory Signal Pathway

Shear stress may be the most crucial local factor affecting atherogenesis. The present study investigated the effect of exposure to increased shear stress promoted by enhanced external counterpulsation (EECP) on the progression of atherosclerosis and the underlying inflammation-related molecular mechanisms in a porcine model of hypercholesterolemia. Hypercholesterolemic pigs were subjected to a 7-week EECP intervention while being fed a high-cholesterol diet. EECP resulted in a 34.38% increase of mean wall shear stress and a significantly lower pulsatility index in the brachial artery. The animals receiving EECP showed a marked reduction in atherosclerotic lesion size in the coronary artery and abdominal aorta compared with the hypercholesterolemic control group, associated with a decrease in macrophage accumulation. The expression of a set of genes involved in inflammation (including C-reactive protein [CRP], complement 3a, vascular cell adhesion molecule-1 [VCAM-1], and inducible nitric oxide synthase), mitogen-activated protein kinase (MAPK)-p38 phosphorylation, and nuclear factor-kappaB (NF-kappaB) activation, was attenuated. These findings suggested that long-term EECP exerts a retarding effect on atherosclerosis by downregulating proinflammatory gene expression. The underlying mechanisms are related to chronic exposure to increased pulsatile shear stress promoted by EECP; this exposure suppresses the overactivation of the MAPK-P38/NF-kappaB/VCAM-1 signaling pathway induced by hypercholesterolemia.

Effect of garlic (Allium sativum) on lipid profiles, antioxidant activity and expression of scavenger receptor class B type I (SR-BI) in liver and intestine of hypercholesterolemic mice

Garlic is one of the medicinal plants, which has shown many useful effects, including Antioxidant activity, hypolipidemic and hypocholesterolemic effects, anti-hypertensive and anti-diabetic effects. Scavenger receptor class B type I (SR-BI) is a cell-surface receptor which mediated selective cholesterol ester uptake from the HDL particle. SR-BI also has an important role in cholesterol absorption in the intestine. Animals were randomly divided into three groups (n=8); group 1: received chow + cholesterol (2%) + cholic acid (0.5%), group 2: chow + 4% (w/w) garlic extract + cholesterol (2%) + cholic acid (0.5%), and group 3: chow only. After one-month mice were sacrificed, blood was collected; lipid profile and blood glucose were determined enzymatically as well as mRNA and protein levels of SR-BI were determined by RT-PCR and westernblot respectively. Compared with hypercholesterolemic control, garlic extract significantly decreased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, Very Low-Density Lipoprotein-Cholesterol (VLDL-C) and atherogenic index (all of them P<0.05). The activity of Super oxide dismutase(SOD), glutathione (GSH) and catalase levels were markedly increased in garlic-treated animals compared with hypercholesterolemic animals (p<0.05). The plasma levels of MDA markedly reduced in garlic group compared with hypercholesterolemic group. Intestinal SR-BI mRNA and protein were significantly decreased in garlic extract mice treatment compared with hypercholesterolemic control. Levels of liver SR-BI protein significantly reduced in hypercholesterolemic group (P<0.05). In conclusion, garlic extract markedly reduced TC, LDL-C, TG, VLDL-C and atherogenic index, as compared with the hypercholesterolemic control group. On the other hand garlic extract led to down-regulation of SR-BI protein and mRNA in the intestine of mice.

Perbaikan Fraksi Lipid Serum Tikus Putih Hiperkolesterolemi Setelah Pemberian Jus dari Berbagai Olahan Tomat (Hypercholesterolemia Albino Rat Lipid Fraction Improvement After Giving Tomato Juice)

This research would like to show the effect of tomato juice in a variety processing method towards hypercholesterolemia albino rat blood plasma lipid fraction. The special purpose if to know and analyze tomato juice advantages towards total cholesterol content, LDL–cholesterol, HDL–cholesterol and triglyceride. The research design is a Post Test Randomized Control Design by means of Complete Randomized Design (RAL). There are 4 groups of treatment, each groups has 6 repeaters. The data is tested by One Way Varian Analyze. If there is a significance difference, there will be Duncan’s New Multiple Range Test followed. The research shows that there is a significance difference of total cholesterol content, LDL–cholesterol, HDL–cholesterol and triglyceride. The highest total cholesterol content, LDL–cholesterol and blood plasma triglyceride content are on the hypercholesterolemia control group. The lowest total cholesterol content, LDL–cholesterol and blood plasma triglyceride content are on the group that is given by a fried tomato juice. The lowest HDL content is on the hypercholesterolemia control group and the highest one are on the group that is given by a fried tomato juice. The research conclusion is that tomato juice supplementation able to fix hypercholesterolemia albino rat blood plasma lipid fraction, especially to decrease total cholesterol content, LDL–cholesterol and blood plasma triglyceride, and increase hypercholesterolemia albino rat blood plasma HDL-cholesterol content. Fried tomato juice give the best effect on decreasing total cholesterol content, LDL–cholesterol and triglyceride and increasing blood plasma HDL-cholesterol content. Keywords: hypercholesterolemia albino rat, total cholesterol content, LDL–cholesterol, HDL–cholesterol, triglyceride

Microarray analysis of gene expression profile in the corpus cavernosum of hypercholesterolemic rats after chronic treatment with PDE5 inhibitor

Gene expression changes in the corpus cavernosum of hypercholesterolemic rats were not fully assessed, which were not previously known to be associated with hypercholesterolemia-related erectile dysfunction (ED). To provide molecular insight into pathophysiology of hypercholesterolemia-related ED and to investigate the effects of Udenafil, a phosphodiesterase type 5 (PDE5) inhibitor, on gene expression, we performed microarray gene expression analysis via gene discovery methods using GenoCheck platinum cDNA chip (Ansan, S. Korea). Sixteen male Sprague-Dawley rats were fed 2% cholesterol diet for 5 months. Half of them were orally treated with Udenafil (20 mg/kg/day) simultaneously. Eight age-matched rats fed normal diet were served as normal control. RNA was extracted from corpus cavernosum and microarray analysis was performed. Decreased erectile responses and hypercholesterolemia were observed in hypercholesterolemic control group. In microarray analysis, 122 candidate genes were noted to be altered based on the magnitude of expression changes, which includes 44 down-regulated and 78 up-regulated genes compared with the age-matched normal controls. These changes were, however, significantly attenuated by treatment with Udenafil. Out of the 78 up-regulated genes, 8 genes were significantly decreased by the chronic treatment with Udenafil. The altered genes were cytochrome oxidase biogenesis protein OXA1, skeletal muscle myosin heavy chain, lipophilin, fast skeletal muscle isoforms beta/alpha, myosin light chain 3, cytochrome c oxidase, adipocyte fatty acid binding protein and one EST gene. In contrast, among the 44 down-regulated genes, Kruppel-like factor 5 and cyclin D1 genes were increased after the Udenafil treatment. These results provide the molecular basis for understanding the pathogenesis of hypercholesterolemia-related ED and offer clues on determining the underlying action mechanism of a PDE5 inhibitor.

BFGF restores endothelium-dependent responses of hypercholesterolemic rabbit thoracic aorta.

In animal models, a hypercholesterolemic diet induces areas of deendothelialization and impairs endothelium-dependent vasorelaxation. Angiogenic growth factors increase endothelial cell growth in vivo. This study was thus designed to test the hypothesis that chronic administration of basic fibroblast growth factor (bFGF) in hypercholesterolemic rabbits might restore normal physiological responses to endothelium-dependent agonists. After feeding on a 2% cholesterol diet for 6 wk, 14 New Zealand White rabbits received twice-weekly intravenous boluses of either 2.5 microg bFGF (hypercholesterolemic bFGF group, n = 6) or placebo (hypercholesterolemic control group, n = 8) for 3 wk and were killed for assessment of in vitro vasoreactivity and for histological analysis. Six animals fed with standard rabbit diet were used to assess normal responses. Endothelium-dependent responses to acetylcholine and to the calcium ionophore A-23187 were reduced in the hypercholesterolemic control group compared with normal rabbits. Hypercholesterolemic animals treated with bFGF had significantly better endothelium-dependent responses than hypercholesterolemic rabbits not treated with bFGF. Endothelium-independent responses did not differ significantly among the three groups. A similar degree of plaque formation was observed in control- and bFGF-treated hypercholesterolemic rabbits. These results show that, in this model of atherosclerosis, bFGF has a highly beneficial effect on the functional responses of atherosclerotic vessels and does not have a deleterious effect on the degree of plaque formation.