title: Enhanced external counterpulsation inhibits intimal hyperplasia by modifying shear stress responsive gene expression in hypercholesterolemic pigs.
abstract: BACKGROUND
  Enhanced external counterpulsation (EECP) is a circulation assist device that may improve endothelial dysfunction by increasing shear stress. Chronic exposure of vascular endothelial cells and vascular smooth muscle cells to relatively high physiological shear stress has antiproliferative and vasoprotective effects. The present study hypothesizes that EECP inhibits intimal hyperplasia and atherogenesis by modifying shear stress-responsive gene expression.
  
  
  RESULTS
  Thirty-five male pigs were randomly assigned to 3 groups: high-cholesterol diet (n=11), high-cholesterol diet plus EECP (n=17), and usual diet (control; n=7). The coronary arteries and aortas were collected for histopathological study and immunohistochemical and Western blot analysis. The peak diastolic arterial wall shear stress during EECP increased significantly compared with before EECP (49.62+/-10.71 versus 23.92+/-7.28 dyne/cm2; P<0.001). Intimal hyperplasia was observed in the coronary arteries of the high-cholesterol diet group, whereas in animals receiving EECP, the intima-to-media area ratio was significantly decreased by 41.59% (21.27+/-10.00% versus 36.41+/-16.69%; P=0.008). Hypercholesterolemia attenuated the protein expression of endothelial NO synthase and enhanced the phosphorylation of extracellular signal-regulated kinases 1/2. EECP treatment alleviated these adverse changes.
  
  
  CONCLUSIONS
  EECP reduces hypercholesterolemia-induced endothelial damage, arrests vascular smooth muscle cell proliferation and migration, decreases proliferating cell nuclear antigen proliferative index, suppresses extracellular matrix formation, and eventually inhibits intimal hyperplasia and the development of atherosclerosis by increasing the arterial wall shear stress, which in turn activates the endothelial NO synthase/NO pathway and probably suppresses extracellular signal-regulated kinases 1/2 overactivation.
authors.affiliation: Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaohong
authors.initials: X
authors.lastname: He
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Donghong
authors.initials: D
authors.lastname: Liu
authors.forename: Jinyun
authors.initials: J
authors.lastname: Luo
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Du
authors.forename: Yafei
authors.initials: Y
authors.lastname: Jin
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiong
authors.forename: Jiangui
authors.initials: J
authors.lastname: He
authors.forename: Dianqiu
authors.initials: D
authors.lastname: Fang
authors.forename: Kuijian
authors.initials: K
authors.lastname: Wang
authors.forename: William E
authors.initials: WE
authors.lastname: Lawson
authors.forename: John C K
authors.initials: JC
authors.lastname: Hui
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Zheng
authors.forename: Guifu
authors.initials: G
authors.lastname: Wu
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000209:etiology / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology; D002455:Cell Division; D002465:Cell Movement; D003324:Coronary Artery Disease / Q000209:etiology / Q000473:pathology*; D015908:Counterpulsation; D004036:Diet, Atherogenic; D004727:Endothelium / Q000473:pathology; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D018056:Hemorheology; D006937:Hypercholesterolemia / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000601:surgery*; D006965:Hyperplasia; D008055:Lipids / Q000097:blood; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011499:Protein Processing, Post-Translational; D011897:Random Allocation; D015398:Signal Transduction; D013314:Stress, Mechanical; D034421:Sus scrofa; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D008055:Lipids; D018809:Proliferating Cell Nuclear Antigen; D052250:Nitric Oxide Synthase Type III; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3