Hypercholesterolemia Inhibits Angiogenesis in Response to Hindlimb Ischemia

Circulation ◽  
2000 ◽  
Vol 102 (suppl_3) ◽  
Author(s):  
Junli Duan ◽  
Toyoaki Murohara ◽  
Hisao Ikeda ◽  
Atsushi Katoh ◽  
Satoshi Shintani ◽  
...  
Keyword(s):  
Blood Flow ◽  
Dietary Intervention ◽  
Laser Doppler ◽  
High Cholesterol Diet ◽  
Standard Diet ◽  
Cholesterol Diet ◽  
Hindlimb Ischemia ◽  
Sprague Dawley ◽  
High Cholesterol ◽  
Arginine Supplementation

Background —Endothelium-derived nitric oxide (EDNO) plays an important role in the regulation of angiogenesis, whereas hypercholesterolemia (HC) impairs EDNO release. We examined the hypothesis that HC may inhibit ischemia-induced angiogenesis by inhibition of EDNO in a rat model of unilateral hindlimb ischemia and that oral l -arginine supplementation, a substrate for NO synthase, may prevent HC-related impairment of angiogenesis. Methods and Results —Male Sprague-Dawley rats were fed (A) standard diet (control), (B) 2% high-cholesterol diet (HC group), or (C) high-cholesterol diet with oral l -arginine (2.25% in drinking water) (HC+L-arg group). At 2 weeks of the dietary intervention, unilateral limb ischemia was surgically induced in all animals. Dietary HC groups (B and C) revealed elevated total and LDL cholesterol levels compared with control animals. Laser Doppler blood flow analyses showed significant decreases in the ischemic/normal limb blood flow ratio in the HC group compared with controls ( P <0.05) when followed up until 4 weeks after surgery. Selective angiography and immunohistochemical analyses in the ischemic limb at postoperative day 14 revealed significantly lower angiographic scores ( P <0.01) and capillary densities ( P <0.01) in the HC group than controls, which were associated with decreased tissue contents of NO x and cGMP. Oral l -arginine supplementation (HC+L-arg) significantly improved all parameters of the laser Doppler blood perfusion ratio, angiographic scores, and capillary densities ( P <0.01 versus HC group), which were accompanied by significant elevations in serum l -arginine levels and tissue NO x and cGMP contents. Conclusions —Collateral vessel formation and angiogenesis in response to hindlimb ischemia were significantly attenuated in rats with dietary HC. The mechanism may be related to the reduced NO bioactivity in the ischemic tissues. Augmentation of the tissue NO activity by oral l -arginine supplementation restored the impaired angiogenesis in HC.

scholarly journals Simvastatin Improves the Jaw Bone Microstructural Defect Induced by High Cholesterol Diet in Rats by Regulating Autophagic Flux

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Jianhua Zhou ◽  
Xiaoli Gao ◽  
Shengyun Huang ◽  
Li Ma ◽  
Yanjun Cui ◽  
...  
Keyword(s):  
High Cholesterol Diet ◽  
Autophagic Flux ◽  
Cholesterol Diet ◽  
Sprague Dawley ◽  
High Cholesterol ◽  
Trabecular Thickness ◽  
Simvastatin Treatment ◽  
Jaw Bone ◽  
Microstructural Defect ◽  
Sprague Dawley Rats

Objective. The objective of this study is to evaluate the effect of simvastatin on the jaw bone microstructural defect and autophagy in rats with high cholesterol diet (HCD). Methods. Male Sprague-Dawley rats were fed a standard rodent chow (NC group) or a high cholesterol diet for 32 weeks and the HCD-fed rats were treated with vehicle (HC group) or simvastatin (5 mg/kg orally daily for 8 weeks, HC + SIM group, and n=10/group). The static histomorphometric changes in the jaw bone tissues in individual rats were evaluated. The relative levels of OPG, RANKL, NF-κB, LC3, and p62 in the jaw bone tissues were determined by quantitative RT-PCR and/or immunohistochemistry. Results. Compared with the NC group, the HC groups had lower trabecular bone volume, trabecular thickness and trabecular number, and increased ratios of RANKL/OPG in the jaw bone, accompanied by enhanced NF-κB activation and autophagy. Simvastatin treatment inhabited these changes, including the decreased levels of serum proinflammatory cytokines and increased autophagy. Conclusion. Simvastatin treatment could inhibit the hyperlipidemia-induced jaw bone microstructural defect in rats by increasing autophagic flux.

scholarly journals Antiatherogenic and Anti-Ischemic Properties of Traditional Chinese Medicine Xinkeshu via Endothelial Protecting Function

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Xu Tao ◽  
Peng Jing-bo ◽  
Zhang Wen-tong ◽  
Zhao Xin ◽  
Zhang Tao-tao ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Myocardial Ischemia ◽  
Probable Mechanism ◽  
High Cholesterol Diet ◽  
Standard Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Diet Model

Including herbal medicine, complementary and alternative medicine (CAM) is popular worldwide. The traditional Chinese medicine xinkeshu has been widely used to treat coronary heart disease in China. This study was designed to investigate the protective effect and probable mechanism of xinkeshu tablet to atherosclerotic myocardial ischemia rabbit. Rabbits were divided into four groups (n=12each) and fed with different diet for 12 weeks: Control (standard diet), Model (high-cholesterol diet), XKS (high-cholesterol diet with 184.8 mg/kg/d xinkeshu), and Atorvastatin (high-cholesterol diet with 5.0 mg/kg/d atorvastatin). Plasma lipoprotein, ECG, endothelium-dependent vessel relaxation, histomorphological study, and expressions of eNOS and VCAM-1 on coronary arteries were assessed. The findings showed that, similar to atorvastatin, xinkeshu presented significant effects on rescuing endothelium-dependent vessel relaxation, inhibiting atherosclerotic progress, preventing myocardial ischemia, and changing eNOS and VCAM-1 expression. However, xinkeshu showed no lipoprotein lowering effect in hypercholesterolemia rabbits. The results of the present study indicated that xinkeshu exerted potent antiatherogenic and anti-ischemic properties on atherosclerotic myocardial ischemia rabbit. An endothelial protecting effect may be involved in the mechanism other than antihyperlipidemic effect.

scholarly journals L-citrulline and L-arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits

2005 ◽  
Vol 102 (38) ◽  
pp. 13681-13686 ◽  
Author(s):  
T. Hayashi ◽  
P. A. R. Juliet ◽  
H. Matsui-Hirai ◽  
A. Miyazaki ◽  
A. Fukatsu ◽  
...  
Keyword(s):  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Arginine Supplementation

scholarly journals POTENTIAL EFFECT OF MACRO ALGA Caulerpa sp. AND Gracilaria sp. EXTRACT LOWERING MALONDIALDEHYDE LEVEL OF WISTAR RATS FED HIGH CHOLESTEROL DIET

2017 ◽  
Vol 5 (1) ◽  
pp. 71
Author(s):  
Ketut Srie Marhaeni Julyasih ◽  
I Gede Putu Wirawan
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Design Research ◽  
Wistar Rat ◽  
Negative Control ◽  
Control Group ◽  
High Cholesterol Diet ◽  
Standard Diet ◽  
Cholesterol Diet ◽  
High Cholesterol

Seaweed has potential nutrient content such as carotenoids, vitamins, fatty acids, carbohydrates, minerals, and other essential substances. Carotenoids have important biological functions as an antioxidant, and immunostimulatory which can prevent the disease, anti-inflammatory, anti-stress, anti-aging, and protect the skin from the harmful effects of ultraviolet radiation. Seaweed generally consumed as a vegetable by people in Bali, known as the local name Bulung Boni (Caulerpa spp.) and Bulung Sangu (Gracilaria spp.).. So far there has been no report or results of research on the effects of extract ethanol of Bulung Boni (Caulerpa sp.) and Bulung Sangu (Gracilaria sp.) as an antioxidant that can prevent lipid peroxidation which can be seen in decreased level of MDA in liver tissue or blood plasma. Therefore it is necessary to determine of plasmaMDA level of Wistar rat after fed high cholesterol diet treated with extract ethanol of Caulerpa sp. and Gracillaria sp. This experimental study used completely randomized design. Research using total of 24 Wistar rats divided into six sample groups of equal size, all fed with a diet high in cholesterol especially in negative control. The study consisted of negative control group (standard diet), positive control group (high cholesterol diet), high-cholesterol diet with Caulerpa sp. extract dose of 20 mg and 60 mg/100 g, high cholesterol diet with Gracilaria sp. extract dose of 20 mg and 60 mg/100 g body weight rat per day.The study resulted that rats fed high cholesterol diet with treated extract ethanol Caulerpa sp. and Gracilaria sp. with a dose of 20 mg and 60 mg per 100 g body weight rat / day had plasma MDA level significantly lower (p <0.05) compared with rats fed high cholesterol diet without treated with extract of Caulerpa sp. and Gracilaria sp.

High-fat and high-cholesterol diet rapidly induces non-alcoholic steatohepatitis with advanced fibrosis in Sprague-Dawley rats

2014 ◽  
Vol 45 (4) ◽  
pp. 458-469 ◽  
Author(s):  
Mayuko Ichimura ◽  
Miku Kawase ◽  
Miki Masuzumi ◽  
Mika Sakaki ◽  
Yasuo Nagata ◽  
...  
Keyword(s):  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
Advanced Fibrosis ◽  
Sprague Dawley ◽  
High Cholesterol ◽  
High Fat ◽  
Alcoholic Steatohepatitis ◽  
Sprague Dawley Rats

Effects of Hypercholesterolaemia on Physiological Recruitment of Coronary Vascular Reserve in Swine

1996 ◽  
Vol 90 (4) ◽  
pp. 261-268 ◽  
Author(s):  
Bruce A. Bergelson ◽  
Tse-Kuan Yu ◽  
Nicholas A. Ruocco
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Oxygen Demand ◽  
High Cholesterol Diet ◽  
Atrial Pacing ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Control Zone ◽  
Vascular Reserve ◽  
Left Anterior Descending Artery

1. The endothelium participates in the regulation of coronary vascular tone. As evidence exists from studies performed on epicardial vessels that hypercholesterolaemia impairs endothelial function, we tested the hypothesis that hypercholesterolaemia impairs coronary vascular reserve in an intact animal. 2. Domestic swine, maintained on a regular (n = 9) or a 2% high-cholesterol (n = 9) diet for 3 months were instrumented with a catheter in the left atrium for microsphere injection, a catheter in the anterior interventricular vein for venous sampling and an 82% stenosis in the left anterior descending artery. Papaverine was used to determine coronary vascular reserve. Regional coronary flow as reflected by perfusion (microsphere measurement), lactate consumption, oxygen consumption and haemodynamics were obtained at baseline, after 10 mg of papaverine and after atrial pacing at a rate of 120 beats/min and 150 beats/min. 3. Cholesterol was elevated in animals on the high cholesterol diet (350 ± 50 mg/dl versus 99 ± 10 mg/dl, P<0.001). Baseline haemodynamics were similar between groups. Baseline transmural flow and its augmentation with papaverine were comparable in the two groups in the control (circumflex) and stenosed (left anterior descending artery) zones. In both groups, perfusion increased in the control zone in response to increased oxygen demand, whereas in the stenosis zone no increase was observed in either group (P not significant for normal versus high cholesterol diet). Endocardial flow reserve in the stenosis zone was exhausted in both groups. Epicardial flow in the stenosis zone increased significantly in the normal (P<0.02) but not in the hypercholesterolaemic animals (P not significant). 4. The endocardial/epicardial ratio in the control zone at baseline revealed greater endocardial dominance in the normal compared with the hypercholesterolaemic animals (1.35 versus 1.10, P<0.01). With papaverine, similar ratios indicated a similar reserve potential in both groups. During increased oxygen demand, normal animals continued to demonstrate endocardial dominance whereas it diminished in the hypercholesterolaemic group. In the stenosis zone, endocardial blood flow dominated at baseline in the normal animals and to a lesser extent in the hypercholesterolaemic animals (1.30 versus 1.10, P = 0.10). During increased oxygen demand, endocardial dominance decreased significantly in both groups of animals; however, it remained greater than 1.0 only in the normal animals. 5. Exposure to elevated cholesterol levels did not impair an animal's ability to augment coronary blood flow in response to an increase in oxygen demand. In contrast to this lack of effect on recruitment of coronary reserve, regional coronary blood flow was altered in the hypercholesterolaemic animals.

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