Peroxisome proliferatoractivated receptor ß/δ regulates cerebral vasospasm after subarachnoid hemorrhage via modulating vascular smooth muscle cells phenotypic conversion.
Mol Med Rep
; 24(6)2021 12.
Article
em En
| MEDLINE
| ID: mdl-34664679
ABSTRACT
Cerebral vasospasm (CVS) is a common complication of subarachnoid hemorrhage (SAH) with high deformity rates and cerebral vascular smooth muscle cells (VSMCs) phenotypic switch is considered to be involved in the regulation of CVS. However, to the best of the authors' knowledge, its underlying molecular mechanism remains to be elucidated. Peroxisome proliferatoractivated receptor ß/δ (PPARß/δ) has been demonstrated to be involved in the modulation of vascular cells proliferation and maintains the autoregulation function of blood vessels. The present study investigated the potential effect of PPARß/δ on CVS following SAH. A model of SAH was established by endovascular perforation on male adult SpragueDawley rats, and the adenovirus PPARß/δ (AdPPARß/δ) was injected via intracerebroventricular administration prior to SAH. The expression levels of phenotypic markers αsmooth muscle actin and embryonic smooth muscle myosin heavy chain were measured via western blotting or immunofluorescence staining. The basilar artery diameter and vessel wall thickness were evaluated under fluorescence microscopy. SAH grade, neurological scores, brain water content and brain swelling were measured to study the mechanisms of PPARß/δ on vascular smooth muscle phenotypic transformation. It was revealed that the expression levels of synthetic proteins were upregulated in rats with SAH and this was accompanied by CVS. Activation of PPARß/δ using AdPPARß/δ markedly upregulated the contractile proteins elevation, restrained the synthetic proteins expression and attenuated SAHinduced CVS by regulating the phenotypic switch in VSMCs at 72 h following SAH. Furthermore, the preliminary study demonstrated that PPARß/δ downregulated ERK activity and decreased the expression of phosphorylated (p)ETS domaincontaining protein Elk1 and pp90 ribosomal S6 kinase, which have been demonstrated to serve an important role in VSMC phenotypic change. Additionally, it was revealed that AdPPARß/δ could positively improve CVS by ameliorating the diameter of the basilar artery and mitigating the thickness of the vascular wall. Furthermore, subsequent experiments demonstrated that AdPPARß/δ markedly reduced the brain water content and brain swelling and improved the neurological outcome. Taken together, the present study identified PPARß/δ as a useful regulator for the VSMCs phenotypic switch and attenuating CVS following SAH, thereby providing novel insights into the therapeutic strategies of delayed cerebral ischemia.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Hemorragia Subaracnóidea
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Vasoespasmo Intracraniano
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PPAR beta
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PPAR delta
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Músculo Liso Vascular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2021
Tipo de documento:
Article