The Role of SIRT3 in Mediating Cardioprotective Effects of RAS Inhibition on Cardiac Ischemia-Reperfusion

Javadov, Sabzali; Escobales, Nelson

doi:10.18433/j3nw2k

Cited by 5 publications

(2 citation statements)

References 26 publications

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“…Ang II receptor antagonists have been implicated in mitochondria protection and the modulation of Ca 2+ signaling through the AT receptors (ATRs) pathway (Javadov and Escobales, 2015). Thus, we aimed to elucidate the expression patterns of the specific AngII receptor subtypes, AT 1 and AT 2 , in NRVMs.…”

Section: Effects Of Mbt On Angii Receptors Pathway In Nrvmsmentioning

confidence: 99%

Cardioprotective effects of Moku-boi-to and its impact on AngII-induced cardiomyocyte hypertrophy

Tagashira,

Abe,

Sato-Numata

et al. 2023

Front. Cell Dev. Biol.

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Cardiomyocyte hypertrophy, induced by elevated levels of angiotensin II (AngII), plays a crucial role in cardiovascular diseases. Current therapeutic approaches aim to regress cardiac hypertrophy but have limited efficacy. Widely used Japanese Kampo medicines are highly safe and potential therapeutic agents. This study aims to explore the impact and mechanisms by which Moku-boi-to (MBT), a Japanese Kampo medicine, exerts its potential cardioprotective benefits against AngII-induced cardiomyocyte hypertrophy, bridging the knowledge gap and contributing to the development of novel therapeutic strategies. By evaluating the effects of six Japanese Kampo medicines with known cardiovascular efficiency on AngII-induced cardiomyocyte hypertrophy and cell death, we identified MBT as a promising candidate. MBT exhibited preventive effects against AngII-induced cardiomyocyte hypertrophy, cell death and demonstrated improvements in intracellular Ca2+ signaling regulation, ROS production, and mitochondrial function. Unexpectedly, experiments combining MBT with the AT1 receptor antagonist losartan suggested that MBT may target the AT1 receptor. In an isoproterenol-induced heart failure mouse model, MBT treatment demonstrated significant effects on cardiac function and hypertrophy. These findings highlight the cardioprotective potential of MBT through AT1 receptor-mediated mechanisms, offering valuable insights into its efficacy in alleviating AngII-induced dysfunction in cardiomyocytes. The study suggests that MBT holds promise as a safe and effective prophylactic agent for cardiac hypertrophy, providing a deeper understanding of its mechanisms for cardioprotection against AngII-induced dysfunction.

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Section: Effects Of Mbt On Angii Receptors Pathway In Nrvmsmentioning

confidence: 99%

Cardioprotective effects of Moku-boi-to and its impact on AngII-induced cardiomyocyte hypertrophy

Tagashira,

Abe,

Sato-Numata

et al. 2023

Front. Cell Dev. Biol.

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“…In addition, the protein deacetylase sirtuin 3 (SIRT3) plays cardinal roles in modulating the metabolic network of fatty acid and glucose metabolism for ATP production [89,90]. Notably, SIRT3 favorably modifies cellular mechanisms implicated in cardiovascular diseases [91,92]. SIRT expression is controlled by PGC-1α and AMPK [93,94] and testosterone activates PGC-1α [95], but it remains unknown whether cardioprotective actions of androgens involve SIRT3 signaling.…”

Section: Signal Transduction Pathways Involved In Shbg Expressionmentioning

confidence: 99%

Classic and Novel Sex Hormone Binding Globulin Effects on the Cardiovascular System in Men

Basualto-Alarcón

García‐Rivas

Troncoso

et al. 2021

International Journal of Endocrinology

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In men, 70% of circulating testosterone binds with high affinity to plasma sex hormone binding globulin (SHBG), which determines its bioavailability in their target cells. In recent years, a growing body of evidence has shown that circulating SHBG not only is a passive carrier for steroid hormones but also actively regulates testosterone signaling through putative plasma membrane receptors and by local expression of androgen-binding proteins apparently to reach local elevated testosterone concentrations in specific androgen target tissues. Circulating SHBG levels are influenced by metabolic and hormonal factors, and they are reduced in obesity and insulin resistance, suggesting that SHBG may have a broader clinical utility in assessing the risk for cardiovascular diseases. Importantly, plasma SHBG levels are strongly correlated with testosterone concentrations, and in men, low testosterone levels are associated with an adverse cardiometabolic profile. Although obesity and insulin resistance are associated with an increased incidence of cardiovascular disease, whether they lead to abnormal expression of circulating SHBG or its interaction with androgen signaling remains to be elucidated. SHBG is produced mainly in the liver, but it can also be expressed in several tissues including the brain, fat tissue, and myocardium. Expression of SHBG is controlled by peroxisome proliferator-activated receptor γ (PPARγ) and AMP-activated protein kinase (AMPK). AMPK/PPAR interaction is critical to regulate hepatocyte nuclear factor-4 (HNF4), a prerequisite for SHBG upregulation. In cardiomyocytes, testosterone activates AMPK and PPARs. Therefore, the description of local expression of cardiac SHBG and its circulating levels may shed new light to explain physiological and adverse cardiometabolic roles of androgens in different tissues. According to emerging clinical evidence, here, we will discuss the potential mechanisms with cardioprotective effects and SHBG levels to be used as an early metabolic and cardiovascular biomarker in men.

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Metabolic Syndrome and Cardiac Remodeling Due to Mitochondrial Oxidative Stress Involving Gliflozins and Sirtuins

et al. 2023

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The Role of SIRT3 in Mediating Cardioprotective Effects of RAS Inhibition on Cardiac Ischemia-Reperfusion

Cited by 5 publications

References 26 publications

Cardioprotective effects of Moku-boi-to and its impact on AngII-induced cardiomyocyte hypertrophy

Cardioprotective effects of Moku-boi-to and its impact on AngII-induced cardiomyocyte hypertrophy

Classic and Novel Sex Hormone Binding Globulin Effects on the Cardiovascular System in Men

Metabolic Syndrome and Cardiac Remodeling Due to Mitochondrial Oxidative Stress Involving Gliflozins and Sirtuins

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