Enhanced external counterpulsation attenuates atherosclerosis progression through modulation of proinflammatory signal pathway.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, China.
Yan
Y
Zhang
Xiaohong
X
He
Donghong
D
Liu
Guifu
G
Wu
Xiaolin
X
Chen
Hong
H
Ma
Zhimin
Z
Du
Yugang
Y
Dong
Yafei
Y
Jin
Wen
W
He
Kuijian
K
Wang
William E
WE
Lawson
John C K
JC
Hui
Zhensheng
Z
Zheng
D000818:Animals; D001018:Aortic Diseases / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D001158:Arteries / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D001783:Blood Flow Velocity; D002097:C-Reactive Protein / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D015926:Complement C3a / Q000235:genetics; D003324:Coronary Artery Disease / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015908:Counterpulsation; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D006937:Hypercholesterolemia / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010766:Phosphorylation; D011673:Pulsatile Flow; D012039:Regional Blood Flow; D015398:Signal Transduction / Q000235:genetics; D013314:Stress, Mechanical; D034421:Sus scrofa; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018836:Inflammation Mediators; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D015926:Complement C3a; D002097:C-Reactive Protein; D002784:Cholesterol; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases