Effects of cyclic strain on vascular cells.

Hemodynamic forces, including shear stress and cyclic strain, have been recognized as important modulators of vascular cell morphology and function. The mechanism by which vascular cells sense and transduce the extracellular mechanical signals into the cell nucleus has only recently begun to come to light. Integrins, ion channels, platelet-derived growth factor receptors, and G proteins have been recognized as mechanosensors, converting the mechanical stimuli into chemical signals. Activation of second messengers, including mitogen-activated protein kinases, protein kinase C, and Akt, follows, leading to an increase in the activity of transcription factors such as activator protein (AP)-1, AP-2, cAMP-responsive element (CRE), early growth response (Egr)-1, and nuclear factor (NF)-kappa B. Binding of these factors to the DNA leads to activation of numerous genes that regulate cell proliferation, apoptosis, differentiation, morphology, migration, and secretory function. Understanding of these responses has provided new insights in the pathogenesis and treatment of vascular diseases, such as atherosclerosis and intimal hyperplasia.