TY - JOUR
T1 - HDAC inhibition as a therapeutic strategy in myocardial ischemia/reperfusion injury
AU - Xie, Min
AU - Tang, Yida
AU - Hill, Joseph A.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health ( HL-120732 , HL-128215 , HL-126012 ), American Heart Association ( 14SFRN20510023 ; 14SFRN20670003 ), Fondation Leducq ( 11CVD04 ), and Cancer Prevention and Research Institute of Texas ( RP110486P3 ) awarded to J.A.H., and grants from the National Institutes of Health ( K08 HL-127305 , R03 HL-141620 ) awarded to M.X.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/4
Y1 - 2019/4
N2 - Reperfusion injury during myocardial infarction accounts for approximately half of final infarct size. Whereas this has been known for decades, efficacious therapy targeting reperfusion injury remains elusive. Many proteins are subject to reversible acetylation, and drugs targeting enzymes that govern these events have emerged in oncology. Among these, small molecules targeting protein deacetylating enzymes, so-called histone deacetylases (HDACs), are approved for human use in rare cancers. Now, work emerging from multiple laboratories, and in both mice and large animals, has documented that HDAC inhibition using compounds approved for clinical use confers robust cardioprotection when delivered at the time of myocardial reperfusion. Here, we summarize the key underpinnings of this science, discuss potential mechanisms, and provide a framework for a first-in-human clinical trial.
AB - Reperfusion injury during myocardial infarction accounts for approximately half of final infarct size. Whereas this has been known for decades, efficacious therapy targeting reperfusion injury remains elusive. Many proteins are subject to reversible acetylation, and drugs targeting enzymes that govern these events have emerged in oncology. Among these, small molecules targeting protein deacetylating enzymes, so-called histone deacetylases (HDACs), are approved for human use in rare cancers. Now, work emerging from multiple laboratories, and in both mice and large animals, has documented that HDAC inhibition using compounds approved for clinical use confers robust cardioprotection when delivered at the time of myocardial reperfusion. Here, we summarize the key underpinnings of this science, discuss potential mechanisms, and provide a framework for a first-in-human clinical trial.
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U2 - 10.1016/j.yjmcc.2019.02.013
DO - 10.1016/j.yjmcc.2019.02.013
M3 - Review article
C2 - 30825484
AN - SCOPUS:85062405852
SN - 0022-2828
VL - 129
SP - 188
EP - 192
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
ER -