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

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 func...

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Published in:Journal of cardiovascular development and disease 2022-08, Vol.9 (8), p.266
Main Authors: Pai, Pei-Ying, Wong, James K. S., Cui, Zhen-Yang, Lin, Yi-Yuan, Lee, Shin-Da
Format: Article
Language:English
Subjects:
Apoptosis
ARBs
Biosynthesis
Blood pressure
caspase
Cell death
Cytochrome
Heart
Hypertension
Insulin-like growth factors
Kinases
Laboratories
Ligands
Mitochondria
peroxisome proliferator-activated receptor-γ
Proteins
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Summary: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.
ISSN:2308-3425
2308-3425
DOI:10.3390/jcdd9080266