Hypertensive vascular remodeling was inhibited by Xuezhikang through the regulation of Fibulin-3 and MMPs in spontaneously hypertensive rats.
Fibulin-3, an extracellular glycoprotein, has been suggested as having functions in vessels. In hypertension, extracellular matrix, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play important roles in cardiovascular remodeling. However, the role of Fibulin-3 as an extracellular glycoprotein in hypertensive vascular remodeling remains unclear. Our study was to determine whether Fibulin-3 and TIMPs/MMPs would affect vascular structure during hypertension and the treatment of Xuezhikang. Thirty spontaneously hypertensive rats (SHRs) aged 8 weeks were randomized to three groups: SHRs control group (SHRs group, n=10), group treated with low dose Xuezhikang (XZK-L, 20 mg/kg/d, n=10) and group treated with high dose Xuezhikang (XZK-H, 200 mg/kg/d, n=10), the normal group was comprised of ten Wistar-Kyoto (WKY) rats of the same age. We showed that serum nitric oxide (NO) in control group was significantly lower than WKY group (P<0.05). Concomitantly, serum oxidized low-density lipoprotein (ox-LDL) was higher than WKY group (P<0.05). The treatment of high dose Xuezhikang significantly dicreased ox-LDL, left ventricular mass index (LVMI) and Wall-to-lumen area ratio (W/L) of thoracic aorta (P<0.05), while serum NO was significantly increasing (P<0.05). Moreover, the expressions of Fibulin-3 and MMP-2, 9 at both protein and mRNA levels were significantly higher in thoracic aorta of SHRs group compared to WKY group by immunohistochemistry and western blotting (P<0.05). However, the levels of Fibulin-3 and MMP-2, 9 were significantly decreased in XZK-H group compared to control group (P<0.05). The level of TIMP-3 had no significance difference between SHRs and WKY groups (P>0.05). So the levels of Fibulin-3 and MMP-2, 9 in SHRs could be inhibited by Xuezhikang. Furthermore, a strong correlation in transcript expression was established between Fibulin-3, and MMP-2 (r=0.81, P<0.05) and MMP-9 (r=0.92, P<0.05) through immunohistochemistry. In summary, the overexpression of Fibulin-3 and MMP-2, 9 levels were associated with hypertension and vascular remodeling and inhibited by Xuezhikang. Fibulin-3 is a candidate in the pathogenesis of cardiovascular remodeling in hypertension.
Graduate School of Southern Medical University Guangzhou, China ; Department of Cardiology, The First Affiliated Hospital of Guangdong Pharmaceutical University Guangzhou, China.
Zhong-Wei
ZW
Lin
Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University Guangzhou, China.
Zhuo
Z
Wang
Department of Cardiology, The First Affiliated Hospital of Guangdong Pharmaceutical University Guangzhou, China.
Gui-Ping
GP
Zhu
Department of Cardiology, The First Affiliated Hospital of Guangdong Pharmaceutical University Guangzhou, China.
Bo-Wei
BW
Li
Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University Guangzhou, China.
Wen-Lin
WL
Xie
Department of Cardiology, Guangzhou General Hospital of Guangzhou Military Command Guangzhou, China.
Ding-Cheng
DC
Xiang
Fibulin-3; hypertension; matrix metalloproteinase; spontaneously hypertensive rat; vascular remodeling