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Am J Physiol Heart Circ Physiol 297: H1535-H1543, 2009. First published August 14, 2009; doi:10.1152/ajpheart.00510.2009
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INNOVATIVE METHODOLOGY

Partial carotid ligation is a model of acutely induced disturbed flow, leading to rapid endothelial dysfunction and atherosclerosis

Douglas Nam,1,* Chih-Wen Ni,2,* Amir Rezvan,1 Jin Suo,2 Klaudia Budzyn,1 Alexander Llanos,1 David Harrison,1 Don Giddens,2 and Hanjoong Jo1,2,3

1Division of Cardiology, Department of Medicine, Emory University, Atlanta; 2Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, Georgia; and 3Department of Bioinspired Science, Ewha Womans University, Seoul, Korea

Submitted June 5, 2009 ; accepted in final form August 4, 2009

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 p47phox-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.

shear stress; endothelial dysfunction; inflammation; atherosclerosis; endothelium


Address for reprint requests and other correspondence: H. Jo, Coulter Dept. of Biomedical Engineering, Emory Univ., WMB 2001, Atlanta, GA 30322 (e-mail: hanjoong.jo{at}bme.gatech.edu).




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