Enhanced External Counterpulsation Inhibits Intimal Hyperplasia by Modifying Shear Stress Responsive Gene Expression in Hypercholesterolemic Pigs

@article{citeulike:1615751, 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 stressresponsive gene expression. Methods and 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. 10.1161/CIRCULATIONAHA.106.647248}, author = {Zhang, Yan and He, Xiaohong and Chen, Xiaolin and Ma, Hong and Liu, Donghong and Luo, Jinyun and Du, Zhimin and Jin, Yafei and Xiong, Yan and He, Jiangui and Fang, Dianqiu and Wang, Kuijian and Lawson, William E. and Hui, John C. and Zheng, Zhensheng and Wu, Guifu }, citeulike-article-id = {1615751}, doi = {http://dx.doi.org/10.1161/CIRCULATIONAHA.106.647248}, journal = {Circulation}, keywords = {cholesterol, diet, enos, erk12, in\_vivo, increase, pig, shear}, month = {July}, number = {5}, pages = {526--534}, posted-at = {2007-09-03 08:08:06}, priority = {2}, title = {Enhanced External Counterpulsation Inhibits Intimal Hyperplasia by Modifying Shear Stress Responsive Gene Expression in Hypercholesterolemic Pigs}, url = {http://dx.doi.org/10.1161/CIRCULATIONAHA.106.647248}, volume = {116}, year = {2007} }

TY - JOUR ID - citeulike:1615751 L3 - citeulike-article-id:1615751 TI - Enhanced External Counterpulsation Inhibits Intimal Hyperplasia by Modifying Shear Stress Responsive Gene Expression in Hypercholesterolemic Pigs JF - Circulation VL - 116 IS - 5 SP - 526 EP - 534 N2 - 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 stressresponsive gene expression. Methods and 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. 10.1161/CIRCULATIONAHA.106.647248 KW - cholesterol KW - diet KW - enos KW - erk12 KW - in_vivo KW - increase KW - pig KW - shear AU - Zhang, Yan AU - He, Xiaohong AU - Chen, Xiaolin AU - Ma, Hong AU - Liu, Donghong AU - Luo, Jinyun AU - Du, Zhimin AU - Jin, Yafei AU - Xiong, Yan AU - He, Jiangui AU - Fang, Dianqiu AU - Wang, Kuijian AU - Lawson, William AU - Hui, John AU - Zheng, Zhensheng AU - Wu, Guifu PY - 2007/07/31/ UR - http://dx.doi.org/10.1161/CIRCULATIONAHA.106.647248 ER -