Angiotensin II Receptor Blocker Irbesartan Enhanced SIRT1 longevity Signaling Replaces the Mitochondrial Biogenetic Survival Pathway to Attenuate Hypertension-Induced Heart Apoptosis

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Title:	Angiotensin II Receptor Blocker Irbesartan Enhanced SIRT1 longevity Signaling Replaces the Mitochondrial Biogenetic Survival Pathway to Attenuate Hypertension-Induced Heart Apoptosis
Authors:	白;Pai, Pei-Ying;黃國書;Wong, Kok-Suh;Cu, Zhen-Yang;Cui, Zhen-Yang;Lin, Yi-Yuan;Lin, Yi-Yuan;李信達;Lee, Shin-Da
Contributors:	醫學暨健康學院醫學檢驗暨生物技術學系
Keywords:	ARBs;caspase;cell death;heart;hypertension;peroxisome proliferator-activated receptor-γ.
Date:	2022-08-01
Issue Date:	2023-03-29 02:03:54 (UTC+0)
Publisher:	亞洲大學
Abstract:	Background: The present study investigated whether angiotensin II type 1 receptor blocker irbesartan (ARB) and partial agonist of PPAR-γ prevents heart apoptosis by suppressing cardiac Fas/FasL-mediated to mitochondria-mediated apoptosis in the hearts of hypertensive rat model. Methods: Cardiac function using echocardiography, H&E staining, TUNEL assay, and Western blotting were measured in the excised hearts from three groups, i.e., an untreated hypertensive group (SHR), an ARB-treated hypertensive group (50 mg/kg/day, S.C., SHR-ARB), and untreated normotensive Wistar-Kyoto rats (WKY). Results: Fas Ligand, Fas death receptors, FADD, active caspase-8, active caspase-3 (Fas/FasL-mediated apoptotic pathway), as well as Bax, cytochrome c, active caspase-9 and -3 (mitochondria-mediated apoptotic pathway), IGF-II, and p-JNK were decreased in SHR-ARB group when compared with the SHR group. SIRT1, PGC-1α, Bcl2, and Bcl-xL (SIRT1/PGC-1α pro-survival pathway) were increased in the SHR-ARB group when compared with the SHR group. Conclusions: Our findings suggested that the ARB might prevent cardiac Fas/FasL-mediated to mitochondria-mediated apoptosis pathway in the hypertensive model associated with IGF-II, p-JNK deactivation, and SIRT1/PGC-1α pro-survival pathway upregulation. ARB prevents hypertension-enhanced cardiac apoptosis via enhancing SIRT1 longevity signaling and enhances the mitochondrial biogenetic survival pathway.
Appears in Collections:	[生物科技學系] 期刊論文

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