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.

ObjectiveCardiac mitochondrial dysfunction was found in ischemic heart disease (IHD). Hence, this study determined the effects of exercise training (ET) on cardiac mitochondrial respiration and cardiac mitochondrial quality control in IHD.MethodsA narrative synthesis was conducted after searching animal studies written in English in three databases (PubMed, Web of Science, and EMBASE) until December 2020. Studies that used aerobic exercise as an intervention for at least 3 weeks and had at least normal, negative (sedentary IHD), and positive (exercise-trained IHD) groups were included. The CAMARADES checklist was used to check the quality of the included studies.ResultsThe 10 included studies (CAMARADES score: 6–7/10) used swimming or treadmill exercise for 3–8 weeks. Seven studies showed that ET ameliorated cardiac mitochondrial respiratory function as manifested by decreased reactive oxygen species (ROS) production and increased complexes I-V activity, superoxide dismutase 2 (SOD2), respiratory control ratio (RCR), NADH dehydrogenase subunits 1 and 6 (ND1/6), Cytochrome B (CytB), and adenosine triphosphate (ATP) production. Ten studies showed that ET improved cardiac mitochondrial quality control in IHD as manifested by enhanced and/or controlled mitochondrial biogenesis, dynamics, and mitophagy. Four other studies showed that ET resulted in better cardiac mitochondrial physiological characteristics.ConclusionExercise training could improve cardiac mitochondrial functions, including respiration, biogenesis, dynamics, and mitophagy in IHD.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=226817, identifier: CRD42021226817.

BackgroundThis review aims to summarize the antiapoptotic, pro-survival, and antifibrotic effects of exercise training in hypertensive hearts.MethodsKeyword searches were conducted in PubMed, Web of Science, and Scopus in May 2021. Research published in English on the effects of exercise training on the apoptosis, survival, and fibrosis pathways in hypertension was included. The CAMARADES checklist was used to determine the quality of the studies. Two reviewers independently implemented predesigned protocols for the search and selection of studies, the assessment of study quality, and the evaluation of the strength of evidence.ResultsEleven studies were included after selection. The duration of the exercise training ranged from 5 to 27 weeks. Nine studies showed that exercise training improved cardiac survival rates by increasing IGF-1, IGF-1 receptor, p-PI3K, Bcl-2, HSP 72, and p-Akt. Furthermore, 10 studies showed that exercise training reduced apoptotic pathways by downregulating Bid, t-Bid, Bad, Bak, Bax, TNF, and FADD. Finally, two studies reported the modification and subsequent improvement of physiological characteristics of fibrosis and decreased MAPK p38 and PTEN levels by exercise training in the left ventricle of the heart.ConclusionsThe findings of the review showed that exercise training could improve cardiac survival rates and attenuate cardiac apoptotic and fibrotic pathways in hypertension, suggesting that exercise training could act as a therapeutic approach to prevent hypertension-induced cardiac apoptosis and fibrosis.Systematic Review Registrationhttps://www.crd.york.ac.uk, identifier: CRD42021254118.