title: Vascular endothelium, hemodynamics, and the pathobiology of atherosclerosis.
abstract: The localization of atherosclerotic lesion formation to regions of disturbed blood flow associated with certain arterial geometries, in humans and experimental animals, suggests an important role for hemodynamic forces in the pathobiology of atherosclerosis. There is increasing evidence that the vascular endothelium, which is directly exposed to various fluid mechanical forces generated by pulsatile blood flow, can discriminate among these different biomechanical stimuli and transduce them into genetic regulatory programs that modulate endothelial function. In this brief review, we discuss how biomechanical stimuli generated by blood flow can influence endothelial functional phenotypes, and explore the working hypothesis of "atheroprone" hemodynamic environments as "local risk factors" in atherogenesis. In addition, we consider the therapeutic implications of the activation of "atheroprotective genes" and their role as "critical regulatory nodes" in vascular homeostasis.
authors: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. mgimbrone@rics.bwh.harvard.edu
authors: Michael A
authors: MA
authors: Gimbrone
authors: Guillermo
authors: G
authors: García-Cardeña
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D001696:Biomechanical Phenomena; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D005786:Gene Expression Regulation; D005838:Genotype; D006439:Hemodynamics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D013314:Stress, Mechanical
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C096161:KLF2 protein, human; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors