The integrin-mediated cyclic strain-induced signaling pathway in vascular endothelial cells.
The irregular distribution of plaque in the vasculature results from the interaction of local hemodynamic forces with the vessel wall. One well-characterized force is cyclic circumferential strain, the repetitive pulsatile pressure distention on the arterial wall. This review summarizes current research, which has aimed to elicit the signal transduction pathway by which cyclic strain elicits functional and structural responses in endothelial cells; specifically, it summarizes the signaling pathway that begins with the reorganization of integrins. One method by which these extracellular matrix receptors affect signal transduction is through their ability to initiate the process of phosphorylation on tyrosine residues of cytoplasmic protein kinases, including focal adhesion kinase. The strain-induced pathway appears to also involve ras and the mitogen-activated protein kinase family of enzymes, and preliminary data suggests a role for src as well. Ultimately, it is the regulation of gene expression through the modulation of transcription factors that allows endothelial cells to respond to changes in local hemodynamics.
Frangos
S G
SG
Section of Vascular Surgery, Yale University School of Medicine, New Haven, CT 06510, USA.
Knox
R
R
Yano
Y
Y
Chen
E
E
Di Luozzo
G
G
Chen
A H
AH
Sumpio
B E
BE
D001794:Blood Pressure / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000502:physiology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011674:Pulse; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical; D014471:Umbilical Veins / Q000502:physiology; D014664:Vasodilation
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