首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Cyclic strain-mediated matrix metalloproteinase regulation within the vascular endothelium: a force to be reckoned with
Authors:Cummins Philip M  von Offenberg Sweeney Nicholas  Killeen Maria T  Birney Yvonne A  Redmond Eileen M  Cahill Paul A
Institution:Vascular Health Research Centre, Faculty of Science and Health, Dublin City Univ., Dublin, Ireland. phil.cummins@dcu.ie
Abstract:The vascular endothelium is a dynamic cellular interface between the vessel wall and the bloodstream, where it regulates the physiological effects of humoral and biomechanical stimuli on vessel tone and remodeling. With respect to the latter hemodynamic stimulus, the endothelium is chronically exposed to mechanical forces in the form of cyclic circumferential strain, resulting from the pulsatile nature of blood flow, and shear stress. Both forces can profoundly modulate endothelial cell (EC) metabolism and function and, under normal physiological conditions, impart an atheroprotective effect that disfavors pathological remodeling of the vessel wall. Moreover, disruption of normal hemodynamic loading can be either causative of or contributory to vascular diseases such as atherosclerosis. EC-matrix interactions are a critical determinant of how the vascular endothelium responds to these forces and unquestionably utilizes matrix metalloproteinases (MMPs), enzymes capable of degrading basement membrane and interstitial matrix molecules, to facilitate force-mediated changes in vascular cell fate. In view of the growing importance of blood flow patterns and mechanotransduction to vascular health and pathophysiology, and considering the potential value of MMPs as therapeutic targets, a timely review of our collective understanding of MMP mechanoregulation and its impact on the vascular endothelium is warranted. More specifically, this review primarily summarizes our current knowledge of how cyclic strain regulates MMP expression and activation within the vascular endothelium and subsequently endeavors to address the direct and indirect consequences of this on vascular EC fate. Possible relevance of these phenomena to vascular endothelial dysfunction and pathological remodeling are also addressed.
Keywords:
本文献已被 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号