PPARβ/δ, a Novel Regulator for Vascular Smooth Muscle Cells Phenotypic Modulation and Vascular Remodeling after Subarachnoid Hemorrhage in Rats

被引：12
作者：
Zhang, Hongrong [1 ]
Jiang, Li [1 ]
Guo, Zongduo [1 ]
Zhong, Jianjun [1 ]
Wu, Jingchuan [1 ]
He, Junchi [1 ]
Liu, Han [1 ]
He, Zhaohui [1 ]
Wu, Haitao [2 ]
Cheng, Chongjie [1 ]
Sun, Xiaochuan [1 ]
机构：
[1] Chongqing Med Univ, Dept Neurosurg, Affiliated Hosp 1, 1 Youyi Rd, Chongqing, Peoples R China
[2] Zunyi Med Coll, Affiliated Hosp, Dept Neurosurg, 149 Dalian Rd, Zunyi, Guizhou, Peoples R China
来源：
SCIENTIFIC REPORTS | 2017年 / 7卷
基金：
中国国家自然科学基金;
关键词：
CEREBRAL AUTOREGULATION; GENE-EXPRESSION; BASILAR ARTERY; ACTIVATION; MYOCARDIN; PROLIFERATION; COACTIVATORS; COFACTOR; PATHWAY; GROWTH;
D O I：
10.1038/srep45234
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Cerebral vascular smooth muscle cell (VSMC) phenotypic switch is involved in the pathophysiology of vascular injury after aneurysmal subarachnoid hemorrhage (aSAH), whereas the molecular mechanism underlying it remains largely speculative. Peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) has been implicated to modulate the vascular cells proliferation and vascular homeostasis. In the present study, we investigated the potential role of PPAR beta/delta in VSMC phenotypic switch following SAH. Activation of PPAR beta/delta by GW0742 and adenoviruses PPAR beta/delta (Ad-PPAR beta/delta) significantly inhibited hemoglobin-induced VSMC phenotypic switch. However, the effects of PPAR beta/delta on VSMC phenotypic switch were partly obstacled in the presence of LY294002, a potent inhibitor of Phosphatidyl-Inositol-3 Kinase-AKT (PI3K/AKT). Furthermore, following study demonstrated that PPAR beta/delta-induced PI3K/AKT activation can also contribute to Serum Response Factor (SRF) nucleus localization and Myocardin expression, which was highly associated with VSMC phenotypic switch. Finally, we found that AdPPAR beta/delta positively modulated vascular remodeling in SAH rats, i.e. the diameter of basilar artery and the thickness of vessel wall. In addition, overexpression of PPAR beta/delta by adenoviruses significantly improved neurological outcome. Taken together, this study identified PPAR beta/delta as a useful regulator for VSMC phenotypic switch and vascular remodeling following SAH, providing novel insights into the therapeutic strategies of delayed cerebral ischemia.
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页数：13
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