title: Profilin-1 promotes the development of hypertension-induced artery remodeling.
abstract: Hypertension is associated with the structural remodeling and stiffening of arteries and is known to increase cardiovascular risk. In the present study, we investigated the effects of overexpression and knock down of profilin-1 on the vascular structural remodeling in spontaneous hypertensive rats (SHRs) using an adenovirus injection to knock down or overexpress profilin-1 mRNA. As a control, blank adenovirus was injected into age-matched SHRs and Wistar-Kyoto rats (WKYs). We quantified arterial structural remodeling through morphological methods, with thoracic aortas stained with hematoxylin-eosin and picosirius red. Western blotting was performed to measure the protein expression of inducible nitric oxide synthase (iNOS) and p38 mitogen-activated protein kinase (p38), and peroxynitrite was quantified by immunohistochemical staining. Overexpression of profilin-1 significantly promoted aortic remodeling, including an increase in vessel size, wall thickness, and collagen content, whereas the knockdown of profilin-1 could reverse these effects. In addition, the expression of phosphorylated p38, iNOS and peroxynitrite was significantly upregulated in SHRs with profilin-1 overexpression along with an increased level of interleukin- 6 (IL-6). These changes could be reversed by knockdown of profilin-1. Our results demonstrate a crucial role for profilin-1 in hypertension-induced arterial structural remodeling at least in part through the p38-iNOS-peroxynitrite pathway.
authors.affiliation: Department of Geriatric Cardiology, Qilu Hospital of Shandong University, Jinan, P.R. China (YW, JZ, HG, SZ, XJ, XL, BY, XL, JQ).
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Haiqing
authors.initials: H
authors.lastname: Gao
authors.forename: Shaohua
authors.initials: S
authors.lastname: Zhao
authors.forename: Xiang
authors.initials: X
authors.lastname: Ji
authors.forename: Xiangju
authors.initials: X
authors.lastname: Liu
authors.forename: Beian
authors.initials: B
authors.lastname: You
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Qiu
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology*; D001835:Body Weight; D005355:Fibrosis; D006973:Hypertension / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D051304:Profilins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051304:Profilins; D030421:Peroxynitrous Acid; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases
keywords: SHR; adenovirus vector; hypertension; profilin-1; vascular remodeling