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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1744.)
© 2007 American Heart Association, Inc.

Vascular Biology

Mechanical Stretch Simulates Proliferation of Venous Smooth Muscle Cells Through Activation of the Insulin-Like Growth Factor-1 Receptor

Jizhong Cheng; Jie Du

From the Division of Nephrology, Baylor College of Medicine, Houston, TX.

Correspondence to Dr. Jie Du, Baylor College of Medicine, Division of Nephrology, One Baylor Plaza, Alkek N-520, Houston, TX 77030. E-mail jdu{at}bcm.edu

Objective— Activation and proliferation of vascular smooth muscle cells (VSMCs) occur in the venous neointima of vein grafts. VSMCs in a grafted vein are subjected to mechanical stretch; our goal is to understand the essential mechanical stretch-regulated signals that influence VSMCs during neointimal formation in vein grafts.

Methods and Results— In cultured vein VSMCs, mechanical stretch induces proliferation and upregulation of both IGF-1 and IGF-1R. Stretch of VSMCs sustained tyrosine phosphorylation of both IGF-1R and its substrate, IRS-1; these responses were related to mechanical stretch-induced activation of Src and autocrine IGF-1 production. Mechanical stretch-activated IGF-1R is functional because there is a prolonged activation of IRS-1-associated phosphatidylinositol-3 kinase (PI3K). When we knocked out IGF-1R, the mechanical stretch-induced increase in VSMC proliferation was blocked. To link mechanical stretch-activated IGF-1R cell signaling to venous VSMC proliferation in vivo, we also studied a vein graft model. Tamoxifen-inducible null deletion of IGF-1R in mice reduced the formation of neointima in the vein graft.

Conclusions— Our results demonstrate for the first time that mechanical stretch activates IGF-1/IGF-1R signals in venous VSMCs, and we have uncovered a signaling pathway that leads to neointima formation in vivo.

In vein VSMCs, mechanical stretch induces proliferation and activation of IGF-1R. Conditional null deletion of IGF-1R in mice reduced the formation of neointima in the vein graft. Our results have uncovered a signaling pathway that leads to neointima formation in vein graft.

Key Words: mechanical stretch • insulin-like growth factor-1 • vascular smooth muscle cell • proliferation • vein grafts

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Emerging Role of IGF-1R in Stretch-Induced Neointimal Hyperplasia in Venous Grafts

Hannah Song, Amy L. Mowbray, Michelle C. Sykes, and Hanjoong Jo
Arterioscler. Thromb. Vasc. Biol. 2007 27: 1679-1681. [Full Text] [PDF]