title: TRPV1 attenuates intracranial arteriole remodeling through inhibiting VSMC phenotypic modulation in hypertension.
abstract: The phenotypic modulation of contractile vascular smooth muscle cell (VSMC) is widely accepted as the pivotal process in the arterial remodeling induced by hypertension. This study aimed to investigate the potential role of transient receptor potential vanilloid type 1 (TRPV1) on regulating VSMC plasticity and intracranial arteriole remodeling in hypertension. Spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats and TRPV1-/-mice on a C57BL/6J background were used. By microscopic observation of the histopathological sections of vessels from hypertensive SHR and age-matched normotensive WKY control rats, we found that hypertension induced arterial remodeling. Decreased α-smooth muscle actin (α-SMA) and SM22α while increased osteopontin (OPN) were observed in aorta and VSMCs derived from SHR compared with those in WKY, and VSMCs derived from SHR upregulated inflammatory factors. TRPV1 activation by capsaicin significantly increased expression of α-SMA and SM22α, reduced expression of OPN, retarded proliferative and migratory capacities and inhibited inflammatory status in VSMCs from SHR, which was counteracted by TRPV1 antagonist 5'-iodoresiniferatoxin (iRTX) combined with capsaicin. TRPV1 activation by capsaicin ameliorated intracranial arteriole remodeling in SHR and deoxycorticosterone acetate (DOCA)-salt hypertensive mice. However, the attenuation of arteriole remodeling by capsaicin was not observed in TRPV1-/-mice. Furthermore, TRPV1 activation significantly decreased the activity of PI3K and phosphorylation level of Akt in SHR-derived VSMCs. Taken together, we provide evidence that TRPV1 activation by capsaicin attenuates intracranial arteriole remodeling through inhibiting VSMC phenotypic modulation during hypertension, which may be at least partly attributed to the suppression PI3K/Akt signaling pathway. These findings highlight the prospect of TRPV1 in prevention and treatment of hypertension.
authors: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, People's Republic of China.|Department of Neurology, Chengdu Military General Hospital, No. 270 Rongdu Avenue, Jinniu District, Chengdu, 610083, Sichuan Province, People's Republic of China.
authors: Ming-Jie
authors: MJ
authors: Zhang
authors: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, People's Republic of China.|Department of Neurology, No. 97 Hospital of PLA, No. 226 Tongshan Road, Yunlong District, Xuzhou, 221004, Jiangsu Province, People's Republic of China.
authors: Yun
authors: Y
authors: Liu
authors: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors: Zi-Cheng
authors: ZC
authors: Hu
authors: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, People's Republic of China.|Department of Neurology, Bethune International Peace Hospital, No. 398 Zhongshan Road, Qiaoxi District, Shijiazhuang, 050082, Hebei Province, People's Republic of China.
authors: Yi
authors: Y
authors: Zhou
authors: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors: Yan
authors: Y
authors: Pi
authors: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors: Lu
authors: L
authors: Guo
authors: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors: Xu
authors: X
authors: Wang
authors: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, People's Republic of China.
authors: Xue
authors: X
authors: Chen
authors: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, People's Republic of China. zhanglilidoctor@163.com.
authors: Jing-Cheng
authors: JC
authors: Li
authors: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, No. 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, People's Republic of China. zhanglilidoctor@163.com.
authors: Li-Li
authors: LL
authors: Zhang
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D007427:Intracranial Pressure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D050916:TRPV Cation Channels / Q000172:deficiency / Q000378:metabolism*; D066253:Vascular Remodeling
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C493922:Trpv1 protein, rat
keywords: Hypertension; Intracranial arteriole; Phenotypic modulation; TRPV1; VSMC