title: A model of disturbed flow-induced atherosclerosis in mouse carotid artery by partial ligation and a simple method of RNA isolation from carotid endothelium.
abstract: Despite the well-known close association, direct evidence linking disturbed flow to atherogenesis has been lacking. We have recently used a modified version of carotid partial ligation methods to show that it acutely induces low and oscillatory flow conditions, two key characteristics of disturbed flow, in the mouse common carotid artery. Using this model, we have provided direct evidence that disturbed flow indeed leads to rapid and robust atherosclerosis development in Apolipoprotein E knockout mouse. We also developed a method of endothelial RNA preparation with high purity from the mouse carotid intima. Using this mouse model and method, we found that partial ligation causes endothelial dysfunction in a week, followed by robust and rapid atheroma formation in two weeks in a hyperlipidemic mouse model along with features of complex lesion formation such as intraplaque neovascularization by four weeks. This rapid in vivo model and the endothelial RNA preparation method could be used to determine molecular mechanisms underlying flow-dependent regulation of vascular biology and diseases. Also, it could be used to test various therapeutic interventions targeting endothelial dysfunction and atherosclerosis in considerably reduced study duration.
authors.affiliation: Department of Medicine, Division of Cardiology, Emory University, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Nam
authors.forename: Chih-Wen
authors.initials: CW
authors.lastname: Ni
authors.forename: Amir
authors.initials: A
authors.lastname: Rezvan
authors.forename: Jin
authors.initials: J
authors.lastname: Suo
authors.forename: Klaudia
authors.initials: K
authors.lastname: Budzyn
authors.forename: Alexander
authors.initials: A
authors.lastname: Llanos
authors.forename: David G
authors.initials: DG
authors.lastname: Harrison
authors.forename: Don P
authors.initials: DP
authors.lastname: Giddens
authors.forename: Hanjoong
authors.initials: H
authors.lastname: Jo
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000503:physiopathology*; D002339:Carotid Arteries / Q000737:chemistry / Q000503:physiopathology / Q000601:surgery; D002340:Carotid Artery Diseases / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000737:chemistry*; D008026:Ligation; D051379:Mice; D012313:RNA / Q000302:isolation & purification*; D017539:Tunica Intima / Q000737:chemistry
chemical_list: D012313:RNA