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

Abstract

Orbital shear stress directly stimulates SMC proliferation in long-term culture in vitro and is mediated, at least partially, by the ERK1/2 pathway. The ERK1/2 pathway may also mediate the orbital shear-stress-stimulated switch from SMC contractile to synthetic phenotype. These results suggest that shear-stress-stimulated SMC proliferation after vascular injury is mediated by a pathway amenable to pharmacologic manipulation.

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

“…The synthetic phenotype of VSMCs is critical for atherosclerosis [14][15][16]. Shear stress regulates VSMC function by changing their phenotypic behaviours, such as cell proliferation and differentiation [17]. VSMC aligns in a shear-stress-dependent manner and is relatively parallel to the shear stress direction in high lamina shear stress regions but is perpendicular to the shear stress direction in low shear stress regions in vitro [18].…”

“…Oscillatory shear stress increases VSMC phenotypic transformation to the synthetic phenotype and then induces proliferation, mainly through activation of the phosphatidylinositol 3 kinase (PI3K)-protein kinase B (Akt) signal transduction pathway [32] and extracellular signal-regulated protein kinase 1/2 (ERK1/2) pathway [17] ( figure 1 and table 1). Hence, the flow pattern is another critical parameter for cell proliferation and migration.…”

“…Shear stress regulates the cell function of VSMCs by affecting gene expression. SS, shear stress; ASMC, aortic smooth muscle cell; TFPI-2, tissue factor pathway inhibitor-2; Dyn, dyn/cm 2 ; PDGF, platelet-derived growth factor; MMP, matrix metalloprotease; HO, haem oxygenase; CO, carbon monoxide; NO, nitric oxide; ERK1/2, extracellular signal-regulated kinase1/2; AKT, protein kinase B; min, minute (or minutes); h, hour (or hours); d, day (or days [17] laminar SS 6 dyn bovine ASMC aligned along the direction of SS [18] physiological SS 12 dyn rat ASMC NO at 12 -24 h SS-suppressed proliferation and migration [19] laminar SS 3, 6 and 9 dyn bovine ASMC high SS inhibits SMC proliferation [20] rsif.royalsocietypublishing.org J. R. Soc. Interface 11: 20130852 c-Jun-mediated signalling [54,56].…”

Fluid dynamic analysis of flow in orbiting dishes and the effects of flow on shear stress and endothelial cellular responses.

“…One of the major advantages of using orbital shaker is that it can be used to study multiple cell responses since many culture dishes can stacked. Further, orbital shear model can be physiologically relevant which can describe the complex, disturbed, and orbital blood flow more accurately after angioplasty compared to laminar blood flow (113).…”

Microfluidic platform for impedance characterization of endothelial cells under fluid shear stress.

“…The endothelium is a single film of connected endothelial cells (ECs) forming the interior layer of all blood vessels [20]. It is involved in many vascular functions including maintaining homeostasis [20]- [23], regulating transport across the vascular wall [7], [24]- [26], and machanotransduction signaling [22], [24], [27]- [29]. Research shows that endothelial cell behavior is strongly influenced by their microenvironment including their interaction with the underlying substrate, the extracellular matrix (ECM), and biochemical and biomechanical cues.…”