title: The role of blood flow in determining the sites of atherosclerotic plaques.
abstract: Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids and inflammatory cells along the inner walls of arteries, and is an underlying cause of cardiovascular disease. Atherosclerotic lesions develop predominantly at branches, bends, and bifurcations in the arterial tree because these sites are exposed to low or disturbed blood flow, which exerts low/oscillatory shear stress on the vessel wall. This mechanical environment alters endothelial cell physiology by enhancing inflammatory activation. In contrast, regions of the arterial tree that are exposed to uniform, unidirectional blood flow and experience high shear stress are protected from inflammation and lesion development. Shear stress is sensed by the endothelium via mechanoreceptors and is subsequently transduced into biochemical signals resulting in modulation of proinflammatory signaling pathways. In this article, we address the molecular mechanisms behind the spatial localization of vascular inflammation and atherosclerosis, with particular focus on studies by our own group of two key proinflammatory signaling pathways, the mitogen-activated protein kinase pathway and the nuclear factor-kappa-B pathway.
authors.affiliation: BHF Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London 2nd Floor, B-Block Hammersmith Campus, Du Cane Road, London W12 0NN UK.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Warboys
authors.forename: Narges
authors.initials: N
authors.lastname: Amini
authors.forename: Amalia
authors.initials: A
authors.lastname: de Luca
authors.forename: Paul C
authors.initials: PC
authors.lastname: Evans