The atherosusceptible endothelium: endothelial phenotypes in complex haemodynamic shear stress regions in vivo

摘要: Atherosclerosis initiates at predictable focal sites and develops to a spatially regional disease with limited distribution. There is compelling evidence that links haemodynamics the localized origin of atherosclerotic lesions. Arterial flow in vivo unsteady, dynamically complex, regionally variable. Sites susceptible atherosclerosis near arterial branches curves are associated regions disturbed blood contain repetitive phases reversal resulting steep multidirectional temporal spatial gradients wall shear stresses. Endothelium atherosusceptible relative protected shows activation endoplasmic reticulum (ER) stress unfolded protein response (UPR), altered expression pro-inflammatory Nuclear Factor kappa B (NFκB) oxidant/antioxidant pathways, low major protective factors, notably endothelial nitric oxide synthase Kruppel-like Factors KLF2 KLF4. At some locations, reactive oxygen species levels significantly elevated. Here we describe flow-related phenotypes identified steady-state outline molecular mechanisms may contribute pre-lesional atherosusceptibility as deduced from complementary cell experiments vitro. We conclude significant local risk factor for induces chronic low-level inflammatory state, an adaptive ensure continued function expense increased susceptibility atherogenesis. Surprisingly, when challenged by short-term hypercholesterolaemia vivo, phenotype was resistant greater expression, suggesting sustained hyperlipidaemia required overcome these characteristics.