Investigating the potential effects of selective histone deacetylase 6 inhibitor ACY1215 on infarct size in rats with cardiac ischemia-reperfusion injury.
Chao Feng Lin,Chao Feng Lin,Chao Feng Lin,Kai Cheng Hsu,Wei Chun HuangFu,Tony Eight Lin,Han Li Huang,Shiow Lin Pan +7 more
TLDR
It is indicated that HDAC6 inhibition by ACY1215 might reduce infarct size in rats with cardiac IR injury possibly through modulating HIF-1α expression and TGF-β and CRP should be useful biomarkers to monitor the use of ACY 1215 in cardiacIR injury.Abstract:
Despite the fact that histone deacetylase (HDAC) inhibitors have been tested to treat various cardiovascular diseases, the effects of selective HDAC6 inhibitor ACY1215 on infarct size during cardiac ischemia-reperfusion (IR) injury still remain unknown. In the present study we aimed to investigate the effects of ACY1215 on infarct size in rats with cardiac IR injury, as well as to examine the association between HDAC6 inhibitors and the gene expression of hypoxia inducible factor-1α (HIF-1α), a key regulator of cellular responses to hypoxia. By using computational analysis of high-throughput expression profiling dataset, the association between HDAC inhibitors (pan-HDAC inhibitors panobinostat and vorinostat, and HDAC6 inhibitor ISOX) and their effects on HIF-1α gene-expression were evaluated. The male Wistar rats treated with ligation of left coronary artery followed by reperfusion were used as a cardiac IR model. ACY1215 (50 mg/kg), pan-HDAC inhibitor MPT0E028 (25 mg/kg), and vehicle were intraperitoneally injected within 5 min before reperfusion. The infarct size in rat myocardium was determined by 2,3,5-triphenyltetrazolium chloride staining. The serum levels of transforming growth factor-β (TGF-β) and C-reactive protein (CRP) were also determined. The high-throughput gene expression assay showed that treatment of ISOX was associated with a more decreased gene expression of HIF-1α than that of panobinostat and vorinostat. Compared to control rats, ACY1215-treated rats had a smaller infarct size (49.75 ± 9.36% vs. 19.22 ± 1.70%, p < 0.05), while MPT0E028-treated rats had a similar infarct size to control rats. ACY-1215- and MPT0E028-treated rats had a trend in decreased serum TGF-β levels, but not statistically significant. ACY1215-treated rats also had higher serum CRP levels compared to control rats (641.6 μg/mL vs. 961.37 ± 64.94 μg/mL, p < 0.05). Our research indicated that HDAC6 inhibition by ACY1215 might reduce infarct size in rats with cardiac IR injury possibly through modulating HIF-1α expression. TGF-β and CRP should be useful biomarkers to monitor the use of ACY1215 in cardiac IR injury.read more
Citations
More filters
Journal ArticleDOI
Role of Selective Histone Deacetylase 6 Inhibitor ACY-1215 in Cancer and Other Human Diseases
TL;DR: ACY- 1215 is the first orally available highly selective HDAC6 inhibitor, and its efficacy and therapeutic effects are being continuously verified, as well as the underlying mechanism, in order to guide the future clinical trials of ACY-1215 and more in-depth mechanism researches.
Journal ArticleDOI
The effect of an adaptation to hypoxia on cardiac tolerance to ischemia/reperfusion.
N. V. Naryzhnaya,Leonid N. Maslov,Ivan Derkachev,Huijie Ma,Yi Zhang,N. Rajendra Prasad,Nirmal Singh,F Fu,Jianming Pei,Akpay Sarybaev,Akylbek Sydykov +10 more
TL;DR: In this paper , a comprehensive overview of how chronic hypoxia enhances cardiac tolerance to ischemia/reperfusion is presented, which can lead to future development of the cardioprotective effect of CH.
Journal ArticleDOI
Degradation of histone deacetylase 6 alleviates ROS-mediated apoptosis in renal ischemia-reperfusion injury.
TL;DR: Wang et al. as mentioned in this paper showed that a selective HDAC6 degrader, proteolysis-targeting chimeras (PROTAC) NP8, could significantly improve renal ischemia reperfusion injury (RIRI).
Journal ArticleDOI
Guanxin V attenuates myocardial ischaemia reperfusion injury through regulating iron homeostasis
Fuqiong Zhou,Zhengguang Zhang,Meiyuan Wang,Weina Zhu,Jie Ruan,Hongyan Long,Yajie Zhang,Ning Gu +7 more
TL;DR: GX can attenuate MIRi via regulating iron homeostasis, indicating that GX may act as a potential candidate for the treatment of MIRI.
Journal ArticleDOI
Targeting histone deacetylases for heart diseases.
TL;DR: In this article , the authors systematically summarize the therapeutic roles of HDAC inhibitors with different chemotypes on heart diseases and discuss the opportunities and challenges in developing HDAC inhibitor for the treatment of cardiac diseases.
References
More filters
Journal ArticleDOI
Functional Discovery via a Compendium of Expression Profiles
Timothy P. Hughes,Matthew J. Marton,Allan R. Jones,Christopher J. Roberts,Roland Stoughton,Christopher D. Armour,Holly A. Bennett,Ernest M. Coffey,Hongyue Dai,Yudong D. He,Matthew J. Kidd,Amy M King,Michael R. Meyer,David J. Slade,Pek Yee Lum,Sergey B. Stepaniants,Daniel D. Shoemaker,Daniel J Gachotte,Kalpana Chakraburtty,Julian A. Simon,Martin Bard,Stephen H. Friend +21 more
TL;DR: A reference database or "compendium" of expression profiles corresponding to 300 diverse mutations and chemical treatments in S. cerevisiae is constructed, and it is shown that the cellular pathways affected can be determined by pattern matching, even among very subtle profiles.
Journal ArticleDOI
A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles.
Aravind Subramanian,Rajiv Narayan,Steven M. Corsello,Steven M. Corsello,David Peck,Ted Natoli,Xiaodong Lu,Joshua Gould,John F. Davis,Andrew A. Tubelli,Jacob K. Asiedu,David L. Lahr,Jodi E. Hirschman,Zihan Liu,Melanie Donahue,Bina Julian,Mariya Khan,David Wadden,Ian Smith,Daniel D. Lam,Arthur Liberzon,Courtney Toder,Mukta Bagul,Marek Orzechowski,Oana M. Enache,Federica Piccioni,Sarah A. Johnson,Nicholas J. Lyons,Alice H. Berger,Alice H. Berger,Alykhan F. Shamji,Angela N. Brooks,Angela N. Brooks,Anita Vrcic,Corey Flynn,Jacqueline Rosains,David Y. Takeda,David Y. Takeda,Roger Hu,Desiree Davison,Justin Lamb,Kristin Ardlie,Larson Hogstrom,Peyton Greenside,Nathanael S. Gray,Nathanael S. Gray,Paul A. Clemons,Serena J. Silver,Xiaoyun Wu,Wen-Ning Zhao,Wen-Ning Zhao,Willis Read-Button,Xiaohua Wu,Stephen J. Haggarty,Stephen J. Haggarty,Lucienne Ronco,Jesse S. Boehm,Stuart L. Schreiber,Stuart L. Schreiber,Stuart L. Schreiber,John G. Doench,Joshua A. Bittker,David E. Root,Bang Wong,Todd R. Golub +64 more
TL;DR: The expanded CMap is reported, made possible by a new, low-cost, high-throughput reduced representation expression profiling method that is shown to be highly reproducible, comparable to RNA sequencing, and suitable for computational inference of the expression levels of 81% of non-measured transcripts.
Journal ArticleDOI
Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis.
TL;DR: Phylogenetic analysis of bacterial HDAC relatives suggests that all three HDAC classes precede the evolution of histone proteins and raises the possibility that the primary activity of some "histone deacetylase" enzymes is directed against non-histone substrates.
Journal ArticleDOI
Cardiac fibrosis in myocardial infarction—from repair and remodeling to regeneration
Virpi Talman,Heikki Ruskoaho +1 more
TL;DR: Current knowledge of the mechanisms of both reparative and reactive cardiac fibrosis in response to myocardial infarction are summarized, the potential of inducing cardiac regeneration through direct reprogramming of fibroblast and myofibroblasts into cardiomyocytes are discussed, and the currently available and potential future therapeutic strategies to inhibit cardiac Fibrosis are reviewed.
Journal ArticleDOI
The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge
Gerd Heusch,Bernard J. Gersh +1 more
TL;DR: The pathophysiology of acute myocardial infarct and reperfusion, notably the temporal and spatial evolution of ischaemic and reperFusion injury, the different modes of cell death, and the resulting coronary microvascular dysfunction are reviewed.