title: Middle cerebral artery alterations in a rat chronic hypoperfusion model.
abstract: Chronic cerebral hypoperfusion (CHP) induces microvascular changes that could contribute to the progression of vascular cognitive impairment and dementia in the aging brain. This study aimed to analyze the effects of CHP on structural, mechanical, and myogenic properties of the middle cerebral artery (MCA) after bilateral common carotid artery occlusion (BCCAO) in adult male Wistar rats. Sham animals underwent a similar surgical procedure without carotid artery (CA) ligation. After 15 days of occlusion, MCA and CA were dissected and MCA structural, mechanical, and myogenic properties were assessed by pressure myography. Collagen I/III expression was determined by immunofluorescence in MCA and CA and by Western blot in CA. mRNA levels for 1A1, 1A2, and 3A1 collagen subunits were quantified by quantitative real-time PCR in CA. Matrix metalloproteinase (MMP-1, MMP-2, MMP-9, and MMP-13) and hypoxia-inducible factor-1α (HIF-1α) protein expression were determined in CA by Western blot. BCCAO diminished cross-sectional area, wall thickness, and wall-to-lumen ratio. Nevertheless, whereas wall stress was increased, stiffness was not modified and myogenic response was diminished. Hypoperfusion triggered HIF-1α expression. Collagen I/III protein expression diminished in MCA and CA after BCCAO, despite increased mRNA levels for 1A1 and 3A1 collagen subunits. Therefore, the reduced collagen expression might be due to proteolytic degradation, since the expression of MMP-1 and MMP-9 increased in the CA. These data suggest that BCCAO induces hypotrophic remodeling by a mechanism that involves a reduction of collagen I/III in association with increased MMP-1 and MMP-9 and that decreases myogenic tone in major arteries supplying the brain.
authors.affiliation: Departament de Farmacologia, Terapèutica i Toxicologia, Institut de Neurociències, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Márquez-Martín
authors.forename: Francesc
authors.initials: F
authors.lastname: Jiménez-Altayó
authors.forename: Ana P
authors.initials: AP
authors.lastname: Dantas
authors.forename: Laura
authors.initials: L
authors.lastname: Caracuel
authors.forename: Anna M
authors.initials: AM
authors.lastname: Planas
authors.forename: Elisabet
authors.initials: E
authors.lastname: Vila
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology*; D017536:Carotid Artery, Common / Q000378:metabolism / Q000503:physiopathology; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D020768:Middle Cerebral Artery / Q000378:metabolism* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D003094:Collagen; D020782:Matrix Metalloproteinases
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