Atherosclerosis is closely associated with disturbed flow characterized by low and oscillatory shear stress, but studies directly linking disturbed flow to atherogenesis is lacking. The major reason for this has been a lack of an animal model in which disturbed flow can be acutely induced and cause atherosclerosis. Here, we characterize partial carotid ligation as a model of disturbed flow with characteristics of low and oscillatory wall shear stress. We also describe a method of isolating intimal RNA in sufficient quantity from mouse carotid arteries. Using this model and method, we found that partial ligation causes upregulation of proatherogenic genes, downregulation of antiatherogenic genes, endothelial dysfunction, and rapid atherosclerosis in 2 wk in a p47(phox)-dependent manner and advanced lesions by 4 wk. We found that partial ligation results in endothelial dysfunction, rapid atherosclerosis, and advanced lesion development in a physiologically relevant model of disturbed flow. It also allows for easy and rapid intimal RNA isolation. This novel model and method could be used for genome-wide studies to determine molecular mechanisms underlying flow-dependent regulation of vascular biology and diseases.
Nam, DouglasNi, Chih-WenRezvan, AmirSuo, JinBudzyn, KlaudiaLlanos, AlexanderHarrison, DavidGiddens, DonJo, HanjoongengHL-75209/HL/NHLBI NIH HHS/HL-87012/HL/NHLBI NIH HHS/R01 HL070531/HL/NHLBI NIH HHS/R01 HL070531-08/HL/NHLBI NIH HHS/UO1HL-80711/HL/NHLBI NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't2009/08/18 09:00Am J Physiol Heart Circ Physiol. 2009 Oct;297(4):H1535-43. doi: 10.1152/ajpheart.00510.2009. Epub 2009 Aug 14.