Open AccessValsartan prevented neointimal hyperplasia and inhibited SRSF1 expression and the TLR4–iNOS–ERK–AT1 receptor pathway in the balloon-injured rat aorta
Author(s) -
Yonghong Li,
Junjie Guo,
Hua Yu,
Xin Liu,
Jingwei Zhou,
Xiangcheng Chu,
Qin Xu,
Tingru Sun,
Liang Peng,
Yang Xi,
Xilong Tang
Publication year - 2021
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.934579
Subject(s) - valsartan , angiotensin ii receptor type 1 , neointimal hyperplasia , nitric oxide synthase , angiotensin ii , medicine , neointima , enos , endocrinology , mapk/erk pathway , receptor , nitric oxide , chemistry , kinase , restenosis , biochemistry , blood pressure , stent
Valsartan has the potential to attenuate neointimal hyperplasia and to suppress the inflammatory response. This study aimed to evaluate the role of valsartan in neointimal hyperplasia and the toll-like receptor 4 (TLR4)-nitric oxide synthase (NOS) pathway in the balloon-injured rat aorta. Forty-eight Wistar rats were randomly allocated to three groups: sham control (control), balloon-injured group (surgery), and balloon-injured+valsartan-treated group (valsartan). Rats were killed at 14 and 28 days after balloon-injury, and then the aortic tissues were collected for morphometric analysis as well as for measurements of the mRNA or protein expression of angiotensin II, angiotensin II type 1 (AT1) receptor, angiotensin II type 2 (AT2) receptor, TLR4, endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), serine/arginine-rich splicing factor 1(SRSF1) and extracellular signal regulated kinase (ERK). Valsartan at a dose of 20 mg/kg/day markedly decreased neointimal hyperplasia in the aorta of balloon-injured rats, and significantly reduced the mRNA or protein expression of TLR4, AT1 receptor, SRSF1 and phosphorylated-ERK (p-ERK) as well as the aortic levels of iNOS (all p<0.05). Moreover, valsartan increased the eNOS level and AT2 receptor mRNA and protein expression levels (all p<0.05). Valsartan prevented neointimal hyperplasia and inhibited SRSF1 expression and the TLR4-iNOS-ERK-AT1 receptor pathway in the balloon-injured rat aorta.