HDAC inhibition as a therapeutic strategy in myocardial ischemia/reperfusion injury

Xie, Min; Tang, Yi‐Da; Hill, Joseph A.

doi:10.1016/j.yjmcc.2019.02.013

Cited by 25 publications

(10 citation statements)

References 48 publications

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“…Class I and II HDAC inhibitors represent a group of small molecule epigenetic modifiers that have demonstrated efficacy in animal models of heart failure over the last decade (Evans and Ferguson, 2018). HDAC inhibition has also been used as a therapeutic strategy for cardiac I/R injury (Xie et al, 2019). Emerging evidence also suggests that inhibition of HDACs protects the heart against myocardial injury and stimulates endogenous angiomyogenesis even in the diabetic heart (Bocchi et al, 2019).…”

Section: β-Ohb Is An Endogenous Hdac Inhibitor and Maintains Mitochondrial Homeostasismentioning

confidence: 99%

Beta-Hydroxybutyrate, Friend or Foe for Stressed Hearts

2021

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One of the characteristics of the failing human heart is a significant alteration in its energy metabolism. Recently, a ketone body, β-hydroxybutyrate (β-OHB) has been implicated in the failing heart’s energy metabolism as an alternative “fuel source.” Utilization of β-OHB in the failing heart increases, and this serves as a “fuel switch” that has been demonstrated to become an adaptive response to stress during the heart failure progression in both diabetic and non-diabetic patients. In addition to serving as an alternative “fuel,” β-OHB represents a signaling molecule that acts as an endogenous histone deacetylase (HDAC) inhibitor. It can increase histone acetylation or lysine acetylation of other signaling molecules. β-OHB has been shown to decrease the production of reactive oxygen species and activate autophagy. Moreover, β-OHB works as an NLR family pyrin domain-containing protein 3 (Nlrp3) inflammasome inhibitor and reduces Nlrp3-mediated inflammatory responses. It has also been reported that β-OHB plays a role in transcriptional or post-translational regulations of various genes’ expression. Increasing β-OHB levels prior to ischemia/reperfusion injury results in a reduced infarct size in rodents, likely due to the signaling function of β-OHB in addition to its role in providing energy. Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been shown to exert strong beneficial effects on the cardiovascular system. They are also capable of increasing the production of β-OHB, which may partially explain their clinical efficacy. Despite all of the beneficial effects of β-OHB, some studies have shown detrimental effects of long-term exposure to β-OHB. Furthermore, not all means of increasing β-OHB levels in the heart are equally effective in treating heart failure. The best timing and therapeutic strategies for the delivery of β-OHB to treat heart disease are unknown and yet to be determined. In this review, we focus on the crucial role of ketone bodies, particularly β-OHB, as both an energy source and a signaling molecule in the stressed heart and the overall therapeutic potential of this compound for cardiovascular diseases.

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Section: β-Ohb Is An Endogenous Hdac Inhibitor and Maintains Mitochondrial Homeostasismentioning

confidence: 99%

Beta-Hydroxybutyrate, Friend or Foe for Stressed Hearts

2021

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“…Similar to our finding, the positive correlation between NFAT and HDACs was also certified by a recent study and was confirmed as key promoter in the regulation of inflammation during the preservation of islet function after islet transplantation [ 27 ]. Besides, inhibition of HDAC1 exerted a neuroprotective effect against cerebral IRI [ 28 , 29 ]. Furthermore, a prior study demonstrated that the increased expression of HDAC1 was partially responsible for the deterioration of mice with HIRI-like symptoms, and its repression acted as a promising therapeutic target for HIRI management [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

PIAS1 Alleviates Hepatic Ischemia-Reperfusion Injury in Mice through a Mechanism Involving NFATc1 SUMOylation

Luo

et al. 2022

Disease Markers

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Recently, attentions have come to the alleviatory effect of protein inhibitor of activated STAT1 (PIAS1) in hepatic ischemia-reperfusion injury (HIRI), but the underlying molecular mechanistic actions remain largely unknown, which were illustrated in the present study. Microarray-based analysis predicted a possible regulatory mechanism involving the PIAS1/NFATc1/HDAC1/IRF-1/p38 MAPK signaling axis in HIRI. Then, growth dynamics of hypoxia/reoxygenation- (H/R-) exposed hepatocytes and liver injury of HIRI-like mice were delineated after the alteration of the PIAS1 expression. We validated that PIAS1 downregulation occurred in H/R-exposed hepatocytes and HIRI-like mice, while the expression of NFATc1, HDAC1, and IRF-1 and phosphorylation levels of p38 were increased. PIAS1 inactivated p38 MAPK signaling by inhibiting HDAC1-mediated IRF-1 through NFATc1 SUMOylation, thereby repressing the inflammatory response and apoptosis of hepatocytes in vitro, and alleviated liver injury in vivo. Collectively, the NFATc1/HDAC1/IRF-1/p38 MAPK signaling axis is highlighted as a promising therapeutic target for potentiating hepatoprotective effects of PIAS1 against HIRI.

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“…Additionally, the protective effect and therapeutic potential of HDACs were verified by cardiac disease pathogenesis, including suppressing cardiac fibrosis; enhancing angiogenesis; preventing electrical remodelling; and regulating apoptosis, autophagy, and cell cycle arrest (Chun, 2020). Studies exhibited that HDAC enzyme suppression has become a potential candidate for decreasing reperfusion impairment (Xie et al, 2019). Ting et al (Zhao et al, 2007) reported the use of trichostatin A (TSA) as an efficient HDAC inhibitor to imitate early pharmacologic preconditioning.…”

Section: Histone Modifications and Hdacs In MImentioning

confidence: 99%

Targeting Epigenetics and Non-coding RNAs in Myocardial Infarction: From Mechanisms to Therapeutics

Chen¹,

Liu²,

Ma³

et al. 2021

Front. Genet.

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Myocardial infarction (MI) is a complicated pathology triggered by numerous environmental and genetic factors. Understanding the effect of epigenetic regulation mechanisms on the cardiovascular disease would advance the field and promote prophylactic methods targeting epigenetic mechanisms. Genetic screening guides individualised MI therapies and surveillance. The present review reported the latest development on the epigenetic regulation of MI in terms of DNA methylation, histone modifications, and microRNA-dependent MI mechanisms and the novel therapies based on epigenetics.

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HDAC inhibition as a therapeutic strategy in myocardial ischemia/reperfusion injury

Cited by 25 publications

References 48 publications

Beta-Hydroxybutyrate, Friend or Foe for Stressed Hearts

Beta-Hydroxybutyrate, Friend or Foe for Stressed Hearts

PIAS1 Alleviates Hepatic Ischemia-Reperfusion Injury in Mice through a Mechanism Involving NFATc1 SUMOylation

Targeting Epigenetics and Non-coding RNAs in Myocardial Infarction: From Mechanisms to Therapeutics

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