EFFECTS OF MECHANICAL FORCES ON SIGNAL-TRANSDUCTION AND GENE-EXPRESSION IN ENDOTHELIAL-CELLS

Fluid shear stress and circumferential stretch play important roles in maintaining the homeostasis of the blood vessel, and they can also be pathophysiological factors in cardiovascular diseases such as atheros clerosis and hypertension. The uses of flow channels and stretch devic es as in vitro models have helped to elucidate the mechanisms of signa l transduction and gene expression in cultured endothelial cells in re sponse to shear stress, which is a function of blood flow and vascular metry, or mechanical strain, which is a function of transmural pressu re and the mechanical properties and geometry of the vessel. Shear str ess has been found to increase the activities of a number of kinases t o modulate the phosphorylation of many signaling proteins in endotheli al cells, eg, the proteins in focal adhesion sites and the proteins in the mitogen-activated protein kinase pathways. Downstream to such sig naling cascades, multiple transcription factors such as AP-1, NF-kappa B, Sp-1, and Egr-1 are activated. The actions of these transcription factors on the corresponding cis-elements result in the induction of g enes encoding for vasoactivators, adhesion molecules, monocyte chemoat tractants, and growth factors in endothelial cells, thus modulating va scular structure and function. Some of the effects of mechanical strai n on endothelial cells are similar to those by shear stress, eg, the s ignaling pathways and the genes activated, but there are differences, eg, the time course of the responses. Studies on the effects of mechan ical forces on signal transduction and gene expression provide insight s into the molecular mechanisms by which hemodynamic factors regulate vascular physiology and pathophysiology.