title: Hyperhomocysteinemia accelerates collagen accumulation in the adventitia of balloon-injured rat carotid arteries via angiotensin II type 1 receptor.
abstract: Recent studies suggest that hyperhomocysteinemia (HHcy) increases collagen type I accumulation in rat vascular adventitia after balloon injury and that Angiotensin II (Ang II) induces collagen synthesis in vascular adventitial fibroblasts. Reports also indicate that Ang II type1 receptor (AT1R) activation, mediated by homocysteine (Hcy) may contribute to collagen type 1 expression in mouse aortic endothelial cells. However, little is known about the possible mechanisms behind the relationship between Hcy and AT1R in adventitial remodeling. Thus, we investigated whether HHcy induces collagen accumulation via activation of AT1R in the adventitia. Male Sprague-Dawley (SD) rats were randomly divided into a control group and a 1% l-methionine-induced HHcy group. Balloon injury was performed after 12 experimental weeks and animals were sacrificed at 7, 14, and 28 days after injury. Collagen deposition and AT1R expression was measured with Western blot. Serum Hcy, adventitial collagen, and AT1R levels were higher in the HHcy group compared with the control group. Hcy time-dependently induced collagen type 1 and AT1R expression, with the highest induction observed at 48 h. Also, we observed that the AT1R blocker, valsartan, attenuated collagen type 1 and AT1R expression. HHcy exacerbates adventitial remodeling after balloon injury, and the underling mechanisms may be related to AT1R activity.
authors.affiliation: Department of Cardiology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District of Beijing, Beijing 100044, China. yaodan-716@163.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Yao
authors.affiliation: Department of Cardiology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District of Beijing, Beijing 100044, China. nlsun@263.net.
authors.forename: Ning-Ling
authors.initials: NL
authors.lastname: Sun
mesh_terms: D063194:Adventitia / Q000378:metabolism*; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D020212:Carotid Artery Injuries / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006710:Homocysteine / Q000378:metabolism / Q000494:pharmacology; D020138:Hyperhomocysteinemia / Q000378:metabolism*; D008297:Male; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D006710:Homocysteine; D003094:Collagen