Enhanced External Counterpulsation Inhibits Intimal Hyperplasia by Modifying Shear Stress–Responsive Gene Expression in Hypercholesterolemic Pigs
| Autor: | Jinyun Luo, Jiangui He, Donghong Liu, Zhimin Du, Yan Xiong, John C.K. Hui, Kuijian Wang, Xiao-hong He, Xiaolin Chen, Hong Ma, Yan Zhang, William Lawson, Yafei Jin, Guifu Wu, Zhensheng Zheng, Dian-qiu Fang |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Intimal hyperplasia Vascular smooth muscle Nitric Oxide Synthase Type III Endothelium Arteriosclerosis Hypercholesterolemia Sus scrofa Aortic Diseases Coronary Artery Disease Muscle Smooth Vascular Random Allocation Cell Movement Counterpulsation Proliferating Cell Nuclear Antigen Physiology (medical) Internal medicine medicine Animals Phosphorylation Endothelial dysfunction Mitogen-Activated Protein Kinase 1 Hyperplasia Mitogen-Activated Protein Kinase 3 business.industry Vascular disease Gene Expression Profiling medicine.disease Tunica intima Lipids Extracellular Matrix Enzyme Activation Endocrinology medicine.anatomical_structure Gene Expression Regulation Hemorheology Diet Atherogenic Female Stress Mechanical Tunica Intima Cardiology and Cardiovascular Medicine business Protein Processing Post-Translational Cell Division Signal Transduction |
| Zdroj: | Circulation. 116:526-534 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circulationaha.106.647248 |
| Popis: | 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. 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/cm 2 ; P 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. |
| Databáze: | OpenAIRE |
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