We are analyzing https://link.springer.com/article/10.1007/s10557-021-07159-1.

Title:
The Protective Role of Bmal1-Regulated Autophagy Mediated by HDAC3/SIRT1 Pathway in Myocardial Ischemia/Reperfusion Injury of Diabetic Rats | Cardiovascular Drugs and Therapy
Description:
Purpose Histone deacetylase 3 (HDAC3) and silent information regulator 1 (SIRT1) are histone deacetylases that regulate important metabolic pathways and play important roles in diabetes and myocardial ischemia/reperfusion (IR) injury. In this study, we explored the protective mechanism of Bmal1-regulated autophagy mediated by the HDAC3/SIRT1 pathway in myocardial IR injury of diabetic rats. Methods and results Type 1 diabetes was established by administering an intraperitoneal injection of streptozotocin. After 8 weeks, the left anterior descending coronary artery was ligated for 30 min and reperfused for 120 min to establish a myocardial IR injury model in diabetic rats. H9c2 cardiomyocytes were exposed to high glucose concentration (30 mM) and hypoxia/reoxygenation (H/R) stimulation in vitro. The myocardial infarct size and levels of serum cTn-I, CK-MB, and LDH in diabetic rats subjected to myocardial IR injury were significantly higher. Upregulated HDAC3 and downregulated SIRT1 expression were observed in diabetic and IR hearts, along with a lower Bmal1 level. Autophagy was rapidly increased in the hearts of diabetic or non-diabetic rats in the IR group compared with the sham group, but significantly attenuated in the hearts of diabetic rats compared with the hearts of non-diabetic rats after IR insult. Consistent with decreased autophagy, we observed increased HDAC3 expression and decreased SIRT1 and Bmal1 levels in the myocardial tissue of diabetic rats after IR. Inhibition of HDAC3 by the inhibitor RGFP966 and activation of SIRT1 by the agonist SRT1720 could significantly attenuate myocardial IR injury in diabetic rats by restoring Bmal1-regulated autophagy. Conclusion Based on these findings, the disordered HDAC3/SIRT1 circuit (upregulated HDAC3 and downregulated SIRT1 levels) plays an important role in aggravating myocardial IR injury in diabetic rats by downregulating Bmal1-mediated autophagy. Treatments targeting HDAC3/SIRT1 to activate the autophagy may represent a novel strategy to alleviate myocardial IR injury in diabetes.
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Keywords {🔍}

pubmed, google, scholar, cas, injury, myocardial, autophagy, diabetic, central, ischemiareperfusion, rats, zhang, article, hdac, sirt, diabetes, role, histone, mol, cell, liu, lei, xia, heart, circadian, pathway, deacetylase, cardiomyocytes, access, mice, privacy, cookies, function, content, data, information, hdacsirt, qiu, glucose, activation, protects, insulin, cardiol, tan, nat, sci, publish, search, cardiovascular, protective,

Topics {✒️}

cardiomyocyte circadia clock differentially influences insulin-mediated processes genetically-obese db/db mice targeting mir-132-3p/hdac3 axis sirt1-nrf-2-ho-1-dependent mechanism sirt1/enos/nf-κb pathway month download article/chapter myocardial ischemia/reperfusion injury myocardial ischemia–reperfusion injury myocardial ischemia-reperfusion injury bmal1-regulated autophagy mediated downregulating bmal1-mediated autophagy zhong-yuan xia sirt1-nrf2 signaling pathway sirt1-dependent autophagy induction ca2+-camkii-regulated induction amp-activated protein kinase hypoxia/reoxygenation-induced injury restoring bmal1-regulated autophagy writing—original draft preparation sirt1-ppars cross-talk disordered hdac3/sirt1 circuit treatments targeting hdac3/sirt1 ischemia/reperfusion injury ischaemic conditioning protocols myocardial ischemia/reperfusion myocardial ischemia reperfusion inhibiting insulin signaling aggravates high glucose myocardial ir injury hypoxic ischemic injury article cardiovascular drugs related subjects restores cardiomyocyte contractility diet-induced obesity full article pdf inducing cardiomyocyte autophagy privacy choices/manage cookies hdac3 mediates cardioprotection prevents cardiac remodeling myocardial infarct size hdac3/sirt1 pathway acute coronary syndrome hypoxia/reoxygenation injury dusp5-erk1/2 pathway lower bmal1 level targeting gsk-3β altered complex activities inhibiting excessive autophagy high glucose concentration systemic glucose homeostasis

Questions {❓}

The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress?

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