Smooth muscle cell signal transduction: implications of vascular biology for vascular surgeons.

Vascular smooth muscle cells exhibit varied responses after vessel injury and surgical interventions, including phenotypic switching, migration, proliferation, protein synthesis, and apoptosis. Although the source of the smooth muscle cells that accumulate in the vascular wall is controversial, possibly reflecting migration from the adventitia, from the circulating blood, or in situ differentiation, the intracellular signal transduction pathways that control these processes are being defined. Some of these pathways include the Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, Rho, death receptor-caspase, and nitric oxide pathways.

Evidence supporting changes in Nogo-B levels as a marker of neointimal expansion but not adaptive arterial remodeling.

Both neointimal hyperplasia and inward remodeling contribute to restenosis and lumen loss. Nogo-B has been recently described as an inhibitor of vascular injury and neointimal hyperplasia. To determine whether Nogo-B expression may be a mediator of inward remodeling, we examine the localization of expression of Nogo-B in an in vivo model that examines both neointimal hyperplasia and inward remodeling.

Sustained orbital shear stress stimulates smooth muscle cell proliferation via the extracellular signal-regulated protein kinase 1/2 pathway.

Objective: Nonlaminar shear stress stimulates smooth muscle cell (SMC) proliferation and migration in vivo, especially after an endothelial-denuding injury. To determine whether sustained shear stress directly stimulates SMC proliferation in vitro, the effect of orbital shear stress on SMC proliferation, phenotype, and extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation was examined.

Methods: Bovine SMCs were exposed to orbital shear stress (210 rpm) for up to 10 days, with and without the ERK1/2 upstream pathway inhibitor PD98059 (10 microM) or the p38 pathway inhibitor SB203580 (10 microM).

Oscillatory shear stress increases smooth muscle cell proliferation and Akt phosphorylation.

Purpose: Hemodynamic forces affect smooth muscle cell (SMC) proliferation and migration both in vitro and in vivo. However, the effects of oscillatory shear stress (SS) on SMC proliferation and signal transduction pathways that control survival are not well described.

Methods: Bovine aortic SMC were exposed to arterial levels of oscillatory SS (14 dyne/cm(2)) with an orbital shaker; control cells were exposed to static conditions (0 dyne/cm(2)).

Arterial wall shear stress: observations from the bench to the bedside.

Shear stress is the tangential force of the flowing blood on the endothelial surface of the blood vessel. Shear is described mathematically or ideal fluids, and in vitro models have enabled researchers to describe the effects of shear on endothelial cells. High shear stress, as found in laminar flow, promotes endothelial cell survival and quiescence, alignment in the direction of flow, and secretion of substances that promote vasodilation and anticoagulation.