The imperatorin derivative OW1, a new vasoactive compound, inhibits VSMC proliferation and extracellular matrix hyperplasia.
Chronic hypertension induces vascular remodeling. The most important factor for hypertension treatment is reducing the risk of cardiovascular disease. OW1 is a novel imperatorin derivative that exhibits vasodilative activity and antihypertensive effects in two-kidney one-clip (2K1C) renovascular hypertensive rats. It also inhibited vascular remodeling of the thoracic aorta in a previous study. Here, the inhibitory effects and mechanisms of OW1 on arterial vascular remodeling were investigated in vitro and in 2K1C hypertensive rats in vivo. OW1 (20μM, 10μM, 5μM) inhibited Ang II-induced vascular smooth muscle cells (VSMCs) proliferation and ROS generation in vitro. OW1 also reversed the Ang II-mediated inhibition of α-SMA levels and stimulation of OPN levels. Histology results showed that treatment of 2K1C hypertensive rats with OW1 (20, 40, and 80mg/kg per day, respectively for 5weeks) in vivo significantly decreased the number of VSMCs, the aortic cross-sectional area (CSA), the media to lumen (M/L) ratio, and the content of collagen I and III in the mesenteric artery. Western blot results also revealed that OW1 stimulated the expression of α-SMA and inhibited the expression of collagen I and III on the thoracic aorta of 2K1C hypertensive rats. In mechanistic studies, OW1 acted as an ACE inhibitor and affected calcium channels. The suppression of MMP expression and the MAPK pathway may account for the effects of OW1 on vascular remodeling. OW1 attenuated vascular remodeling in vitro and in vivo. It could be a novel candidate for hypertension intervention.
School of Medicine, Xi'an Jiaotong University, No. 76, Yanta West Road, #54, Xi'an, Shaanxi Province 710061, PR China.
Nan
N
Zhou
School of Medicine, Xi'an Jiaotong University, No. 76, Yanta West Road, #54, Xi'an, Shaanxi Province 710061, PR China.
Yu
Y
Zhang
School of Medicine, Xi'an Jiaotong University, No. 76, Yanta West Road, #54, Xi'an, Shaanxi Province 710061, PR China.
Tao
T
Wang
School of Medicine, Xi'an Jiaotong University, No. 76, Yanta West Road, #54, Xi'an, Shaanxi Province 710061, PR China.
Jianyu
J
He
School of Medicine, Xi'an Jiaotong University, No. 76, Yanta West Road, #54, Xi'an, Shaanxi Province 710061, PR China.
Huaizhen
H
He
School of Medicine, Xi'an Jiaotong University, No. 76, Yanta West Road, #54, Xi'an, Shaanxi Province 710061, PR China. Electronic address: helc@mail.xjtu.edu.cn.
Langchong
L
He
D000199:Actins / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D015220:Calcium Channels / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D011564:Furocoumarins / Q000494:pharmacology*; D006965:Hyperplasia / Q000188:drug therapy* / Q000378:metabolism; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D000804:Angiotensin II; D000959:Antihypertensive Agents; D015220:Calcium Channels; D024042:Collagen Type I; D024061:Collagen Type III; D011564:Furocoumarins; D020782:Matrix Metalloproteinases; D020928:Mitogen-Activated Protein Kinases; C498862:Acta2 protein, rat; C031534:imperatorin
2K1C hypertensive rats; Ang II generation; Calcium channel; Imperatorin derivative-OW1; ROS generation; Vascular remodeling