Role of integrins in endothelial mechanosensing of shear stress.
The focal pattern of atherosclerotic lesions in arterial vessels suggests that local blood flow patterns are important factors in atherosclerosis. Although disturbed flows in the branches and curved regions are proatherogenic, laminar flows in the straight parts are atheroprotective. Results from in vitro studies on cultured vascular endothelial cells with the use of flow channels suggest that integrins and the associated RhoA small GTPase play important roles in the mechanotransduction mechanism by which shear stress is converted to cascades of molecular signaling to modulate gene expression. By interacting dynamically with extracellular matrix proteins, the mechanosensitive integrins activate RhoA and many signaling molecules in the focal adhesions and cytoplasm. Through such mechanotransduction mechanisms, laminar shear stress upregulates genes involved in antiapoptosis, cell cycle arrest, morphological remodeling, and NO production, thus contributing to the atheroprotective effects. This review summarizes some of the recent findings relevant to these mechanotransduction mechanisms. These studies show that integrins play an important role in mechanosensing in addition to their involvement in cell attachment and migration.
Shyy
John Y-J
JY
Division of Biomedical Sciences, University of California-Riverside, Riverside, Calif 92521-0121, USA. john.shyy@ucr.edu
Chien
Shu
S
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D016023:Integrins / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013314:Stress, Mechanical; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D016023:Integrins; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D020742:rhoA GTP-Binding Protein