title: A simplified murine intimal hyperplasia model founded on a focal carotid stenosis.
abstract: Murine models offer a powerful tool for unraveling the mechanisms of intimal hyperplasia and vascular remodeling, although their technical complexity increases experimental variability and limits widespread application. We describe a simple and clinically relevant mouse model of arterial intimal hyperplasia and remodeling. Focal left carotid artery (LCA) stenosis was created by placing 9-0 nylon suture around the artery using an external 35-gauge mandrel needle (middle or distal location), which was then removed. The effect of adjunctive diet-induced obesity was defined. Flowmetry, wall strain analyses, biomicroscopy, and histology were completed. LCA blood flow sharply decreased by ∼85%, followed by a responsive right carotid artery increase of ∼71%. Circumferential strain decreased by ∼2.1% proximal to the stenosis in both dietary groups. At 28 days, morphologic adaptations included proximal LCA intimal hyperplasia, which was exacerbated by diet-induced obesity. The proximal and distal LCA underwent outward and negative inward remodeling, respectively, in the mid-focal stenosis (remodeling indexes, 1.10 and 0.53). A simple, defined common carotid focal stenosis yields reproducible murine intimal hyperplasia and substantial differentials in arterial wall adaptations. This model offers a tool for investigating mechanisms of hemodynamically driven intimal hyperplasia and arterial wall remodeling.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Tao
authors.forename: Christine R
authors.initials: CR
authors.lastname: Mauro
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.forename: John T
authors.initials: JT
authors.lastname: Favreau
authors.forename: Binh
authors.initials: B
authors.lastname: Nguyen
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Gaudette
authors.forename: C Keith
authors.initials: CK
authors.lastname: Ozaki
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D017536:Carotid Artery, Common / Q000473:pathology* / Q000503:physiopathology; D016893:Carotid Stenosis / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D006965:Hyperplasia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009765:Obesity / Q000150:complications; D012039:Regional Blood Flow; D013312:Stress, Physiological; D017539:Tunica Intima / Q000473:pathology*