Atherosclerotic lesions tend to develop in regions where there are separations from unidirectional laminar blood flow, typically near branches, bifurcations, regions of arterial narrowing, and curvatures in the arteries (1, 2). Obviously, homodynamic forces play a key role in atherosclerosis. Studies also indicate that vascular endothelium function disturbance, especially impairment of endothelium dependent vasodilation, is involved (3). Shear stress affects endothelial cells in many ways, such as cytoskeletal rearrangement, decrease of intracellular pH, release of PGI2 and some growth factors (PDGF, FGF, ECGF, TGF-b, etc), activation of IP3 and mitogen-activated protein kinases, and the significant increase in the production of nitric oxide (1,2,4,5). As an important function factor of vascular endothelial cells, nitric oxide (NO) is closely related to the endothelial dysfunction and atherosclerosis (6). Endothelial derived nitric oxide involves in many events in the vasculature, including vasodilation, inhibition of platelet aggregation, adhesion molecule expression, and vascular smooth muscle proliferation, which are directly or indirectly related to atherosclerosis. Endothelial cells release NO more potently in response to increased shear stress than to agonists that raise intracellular free calcium concentration [Ca2+]i. Studies have indicated that NO production increases with a calcium/CaM dependent manner in the first few minutes after exposed to shear stress, followed by a sustained NO production that occurs more than 30min which is Ca2+ independent (7). The activation of eNOS by shear stress, which modulated by Ca/CaM, G protein, tyrosine kinase phosphorylation and eNOS gene expression, is responsible for the increase of NO production (8). However, the contribution of extracellular calcium to the production of NO is somewhat contradictory.

This content is only available via PDF.
You do not currently have access to this content.