Partial carotid ligation is a model of acutely induced disturbed flow, leading to rapid endothelial dysfunction and atherosclerosis.
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
Douglas
D
Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, USA.
Ni
Chih-Wen
CW
Rezvan
Amir
A
Suo
Jin
J
Budzyn
Klaudia
K
Llanos
Alexander
A
Harrison
David
D
Giddens
Don
D
Jo
Hanjoong
H
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D002340:Carotid Artery Diseases / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D003198:Computer Simulation; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005786:Gene Expression Regulation; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008955:Models, Cardiovascular; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics; D012313:RNA / Q000302:isolation & purification; D012039:Regional Blood Flow; D013314:Stress, Mechanical; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D001057:Apolipoproteins E; D004041:Dietary Fats; D014665:Vasodilator Agents; D013481:Superoxides; D012313:RNA; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1
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