PPARβ/δ, a Novel Regulator for Vascular Smooth Muscle Cells Phenotypic Modulation and Vascular Remodeling after Subarachnoid Hemorrhage in Rats.
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 β/δ (PPARβ/δ) has been implicated to modulate the vascular cells proliferation and vascular homeostasis. In the present study, we investigated the potential role of PPARβ/δ in VSMC phenotypic switch following SAH. Activation of PPARβ/δ by GW0742 and adenoviruses PPARβ/δ (Ad-PPARβ/δ) significantly inhibited hemoglobin-induced VSMC phenotypic switch. However, the effects of PPARβ/δ 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 PPARβ/δ-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 Ad-PPARβ/δ positively modulated vascular remodeling in SAH rats, i.e. the diameter of basilar artery and the thickness of vessel wall. In addition, overexpression of PPARβ/δ by adenoviruses significantly improved neurological outcome. Taken together, this study identified PPARβ/δ as a useful regulator for VSMC phenotypic switch and vascular remodeling following SAH, providing novel insights into the therapeutic strategies of delayed cerebral ischemia.
Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, NO. 1 of Youyi Rd, Yuzhong District, Chongqing, China.
Hongrong
H
Zhang
Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, NO. 1 of Youyi Rd, Yuzhong District, Chongqing, China.
Li
L
Jiang
Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, NO. 1 of Youyi Rd, Yuzhong District, Chongqing, China.
Zongduo
Z
Guo
Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, NO. 1 of Youyi Rd, Yuzhong District, Chongqing, China.
Jianjun
J
Zhong
Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, NO. 1 of Youyi Rd, Yuzhong District, Chongqing, China.
Jingchuan
J
Wu
Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, NO. 1 of Youyi Rd, Yuzhong District, Chongqing, China.
Junchi
J
He
Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, NO. 1 of Youyi Rd, Yuzhong District, Chongqing, China.
Han
H
Liu
Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, NO. 1 of Youyi Rd, Yuzhong District, Chongqing, China.
Zhaohui
Z
He
Department of Neurosurgery, the Affiliated Hospital of Zunyi Medical College, NO. 149 of Dalian Rd, Zunyi, Guizhou, China.
Haitao
H
Wu
Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, NO. 1 of Youyi Rd, Yuzhong District, Chongqing, China.
Chongjie
C
Cheng
Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, NO. 1 of Youyi Rd, Yuzhong District, Chongqing, China.
Xiaochuan
X
Sun
D000818:Animals; D002867:Chromones / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D047494:PPAR delta / Q000378:metabolism*; D048068:PPAR-beta / Q000378:metabolism*; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000378:metabolism* / Q000473:pathology; D066253:Vascular Remodeling
D002867:Chromones; D009025:Morpholines; D047494:PPAR delta; D048068:PPAR-beta; D047428:Protein Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one