A carvedilol-responsive microRNA, miR-125b-5p protects the heart from acute myocardial infarction by repressing pro-apoptotic bak1 and klf13 in cardiomyocytes

Ahmed S. Bayoumi; Kyoung mi Park; Yongchao Wang; Jian peng Teoh; Tatsuya Aonuma; Yao Liang Tang; Huabo Su; Neal Lee Weintraub; Il-man Kim

doi:10.1016/j.yjmcc.2017.11.003

A carvedilol-responsive microRNA, miR-125b-5p protects the heart from acute myocardial infarction by repressing pro-apoptotic bak1 and klf13 in cardiomyocytes

Ahmed S. Bayoumi, Kyoung mi Park, Yongchao Wang, Jian peng Teoh, Tatsuya Aonuma, Yao Liang Tang, Huabo Su, Neal Lee Weintraub, Il-man Kim

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

Abstract

Background Cardiac injury is accompanied by dynamic changes in the expression of microRNAs (miRs), small non-coding RNAs that post-transcriptionally regulate target genes. MiR-125b-5p is downregulated in patients with end-stage dilated and ischemic cardiomyopathy, and has been proposed as a biomarker of heart failure. We previously reported that the β-blocker carvedilol promotes cardioprotection via β-arrestin-biased agonism of β₁-adrenergic receptor while stimulating miR-125b-5p processing in the mouse heart. We hypothesize that β₁-adrenergic receptor/β-arrestin1-responsive miR-125b-5p confers the improvement of cardiac function and structure after acute myocardial infarction. Methods and results Using cultured cardiomyocyte (CM) and in vivo approaches, we show that miR-125b-5p is an ischemic stress-responsive protector against CM apoptosis. CMs lacking miR-125b-5p exhibit increased susceptibility to stress-induced apoptosis, while CMs overexpressing miR-125b-5p have increased phospho-AKT pro-survival signaling. Moreover, we demonstrate that loss-of-function of miR-125b-5p in the mouse heart causes abnormalities in cardiac structure and function after acute myocardial infarction. Mechanistically, the improvement of cardiac function and structure elicited by miR-125b-5p is in part attributed to repression of the pro-apoptotic genes Bak1 and Klf13 in CMs. Conclusions In conclusion, these findings reveal a pivotal role for miR-125b-5p in regulating CM survival during acute myocardial infarction.

Original language	English (US)
Pages (from-to)	72-82
Number of pages	11
Journal	Journal of molecular and cellular cardiology
Volume	114
DOIs	https://doi.org/10.1016/j.yjmcc.2017.11.003
State	Published - Jan 2018

Keywords

Apoptotic genes
Biased G protein-coupled receptor signaling
Cardioprotection
MicroRNAs
β-arrestin

ASJC Scopus subject areas

Molecular Biology
Cardiology and Cardiovascular Medicine

Access to Document

10.1016/j.yjmcc.2017.11.003

Cite this

Bayoumi, A. S., Park, K. M., Wang, Y., Teoh, J. P., Aonuma, T., Tang, Y. L., Su, H., Weintraub, N. L., & Kim, I. (2018). A carvedilol-responsive microRNA, miR-125b-5p protects the heart from acute myocardial infarction by repressing pro-apoptotic bak1 and klf13 in cardiomyocytes. Journal of molecular and cellular cardiology, 114, 72-82. https://doi.org/10.1016/j.yjmcc.2017.11.003

Bayoumi, AS, Park, KM, Wang, Y, Teoh, JP, Aonuma, T, Tang, YL , Su, H , Weintraub, NL & Kim, I 2018, 'A carvedilol-responsive microRNA, miR-125b-5p protects the heart from acute myocardial infarction by repressing pro-apoptotic bak1 and klf13 in cardiomyocytes', Journal of molecular and cellular cardiology, vol. 114, pp. 72-82. https://doi.org/10.1016/j.yjmcc.2017.11.003

@article{71b1d6d98032495aba2e9a75fcce5fc2,

title = "A carvedilol-responsive microRNA, miR-125b-5p protects the heart from acute myocardial infarction by repressing pro-apoptotic bak1 and klf13 in cardiomyocytes",

abstract = "Background Cardiac injury is accompanied by dynamic changes in the expression of microRNAs (miRs), small non-coding RNAs that post-transcriptionally regulate target genes. MiR-125b-5p is downregulated in patients with end-stage dilated and ischemic cardiomyopathy, and has been proposed as a biomarker of heart failure. We previously reported that the β-blocker carvedilol promotes cardioprotection via β-arrestin-biased agonism of β1-adrenergic receptor while stimulating miR-125b-5p processing in the mouse heart. We hypothesize that β1-adrenergic receptor/β-arrestin1-responsive miR-125b-5p confers the improvement of cardiac function and structure after acute myocardial infarction. Methods and results Using cultured cardiomyocyte (CM) and in vivo approaches, we show that miR-125b-5p is an ischemic stress-responsive protector against CM apoptosis. CMs lacking miR-125b-5p exhibit increased susceptibility to stress-induced apoptosis, while CMs overexpressing miR-125b-5p have increased phospho-AKT pro-survival signaling. Moreover, we demonstrate that loss-of-function of miR-125b-5p in the mouse heart causes abnormalities in cardiac structure and function after acute myocardial infarction. Mechanistically, the improvement of cardiac function and structure elicited by miR-125b-5p is in part attributed to repression of the pro-apoptotic genes Bak1 and Klf13 in CMs. Conclusions In conclusion, these findings reveal a pivotal role for miR-125b-5p in regulating CM survival during acute myocardial infarction.",

keywords = "Apoptotic genes, Biased G protein-coupled receptor signaling, Cardioprotection, MicroRNAs, β-arrestin",

author = "Bayoumi, {Ahmed S.} and Park, {Kyoung mi} and Yongchao Wang and Teoh, {Jian peng} and Tatsuya Aonuma and Tang, {Yao Liang} and Huabo Su and Weintraub, {Neal Lee} and Il-man Kim",

note = "Funding Information: This work was supported by American Heart Association Predoctoral Fellowship 16PRE30210016 to Jian-peng Teoh, National Institutes of Health R01 HL086555 to Yaoliang Tang, National Institutes of Health R01 HL124248 to Huabo Su, National Institutes of Health R01 HL134354 and AR070029 to Yaoliang Tang and Neal L. Weintraub, National Institutes of Health R01 HL112640 and HL126949 to Neal L. Weintraub, and American Physiological Society ( APHYS00008 ) Shih-Chun Wang Young Investigator Award, American Heart Association Grant-in-Aid 12GRNT12100048 and Scientist Development Grant 14SDG18970040 , and National Institutes of Health R01 HL124251 to Il-man Kim. Publisher Copyright: {\textcopyright} 2017 Elsevier Ltd",

year = "2018",

month = jan,

doi = "10.1016/j.yjmcc.2017.11.003",

language = "English (US)",

volume = "114",

pages = "72--82",

journal = "Journal of Molecular and Cellular Cardiology",

issn = "0022-2828",

publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - A carvedilol-responsive microRNA, miR-125b-5p protects the heart from acute myocardial infarction by repressing pro-apoptotic bak1 and klf13 in cardiomyocytes

AU - Bayoumi, Ahmed S.

AU - Park, Kyoung mi

AU - Wang, Yongchao

AU - Teoh, Jian peng

AU - Aonuma, Tatsuya

AU - Tang, Yao Liang

AU - Su, Huabo

AU - Weintraub, Neal Lee

AU - Kim, Il-man

N1 - Funding Information: This work was supported by American Heart Association Predoctoral Fellowship 16PRE30210016 to Jian-peng Teoh, National Institutes of Health R01 HL086555 to Yaoliang Tang, National Institutes of Health R01 HL124248 to Huabo Su, National Institutes of Health R01 HL134354 and AR070029 to Yaoliang Tang and Neal L. Weintraub, National Institutes of Health R01 HL112640 and HL126949 to Neal L. Weintraub, and American Physiological Society ( APHYS00008 ) Shih-Chun Wang Young Investigator Award, American Heart Association Grant-in-Aid 12GRNT12100048 and Scientist Development Grant 14SDG18970040 , and National Institutes of Health R01 HL124251 to Il-man Kim. Publisher Copyright: © 2017 Elsevier Ltd

PY - 2018/1

Y1 - 2018/1

N2 - Background Cardiac injury is accompanied by dynamic changes in the expression of microRNAs (miRs), small non-coding RNAs that post-transcriptionally regulate target genes. MiR-125b-5p is downregulated in patients with end-stage dilated and ischemic cardiomyopathy, and has been proposed as a biomarker of heart failure. We previously reported that the β-blocker carvedilol promotes cardioprotection via β-arrestin-biased agonism of β1-adrenergic receptor while stimulating miR-125b-5p processing in the mouse heart. We hypothesize that β1-adrenergic receptor/β-arrestin1-responsive miR-125b-5p confers the improvement of cardiac function and structure after acute myocardial infarction. Methods and results Using cultured cardiomyocyte (CM) and in vivo approaches, we show that miR-125b-5p is an ischemic stress-responsive protector against CM apoptosis. CMs lacking miR-125b-5p exhibit increased susceptibility to stress-induced apoptosis, while CMs overexpressing miR-125b-5p have increased phospho-AKT pro-survival signaling. Moreover, we demonstrate that loss-of-function of miR-125b-5p in the mouse heart causes abnormalities in cardiac structure and function after acute myocardial infarction. Mechanistically, the improvement of cardiac function and structure elicited by miR-125b-5p is in part attributed to repression of the pro-apoptotic genes Bak1 and Klf13 in CMs. Conclusions In conclusion, these findings reveal a pivotal role for miR-125b-5p in regulating CM survival during acute myocardial infarction.

AB - Background Cardiac injury is accompanied by dynamic changes in the expression of microRNAs (miRs), small non-coding RNAs that post-transcriptionally regulate target genes. MiR-125b-5p is downregulated in patients with end-stage dilated and ischemic cardiomyopathy, and has been proposed as a biomarker of heart failure. We previously reported that the β-blocker carvedilol promotes cardioprotection via β-arrestin-biased agonism of β1-adrenergic receptor while stimulating miR-125b-5p processing in the mouse heart. We hypothesize that β1-adrenergic receptor/β-arrestin1-responsive miR-125b-5p confers the improvement of cardiac function and structure after acute myocardial infarction. Methods and results Using cultured cardiomyocyte (CM) and in vivo approaches, we show that miR-125b-5p is an ischemic stress-responsive protector against CM apoptosis. CMs lacking miR-125b-5p exhibit increased susceptibility to stress-induced apoptosis, while CMs overexpressing miR-125b-5p have increased phospho-AKT pro-survival signaling. Moreover, we demonstrate that loss-of-function of miR-125b-5p in the mouse heart causes abnormalities in cardiac structure and function after acute myocardial infarction. Mechanistically, the improvement of cardiac function and structure elicited by miR-125b-5p is in part attributed to repression of the pro-apoptotic genes Bak1 and Klf13 in CMs. Conclusions In conclusion, these findings reveal a pivotal role for miR-125b-5p in regulating CM survival during acute myocardial infarction.

KW - Apoptotic genes

KW - Biased G protein-coupled receptor signaling

KW - Cardioprotection

KW - MicroRNAs

KW - β-arrestin

UR - http://www.scopus.com/inward/record.url?scp=85033405069&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85033405069&partnerID=8YFLogxK

U2 - 10.1016/j.yjmcc.2017.11.003

DO - 10.1016/j.yjmcc.2017.11.003

M3 - Article

C2 - 29122578

AN - SCOPUS:85033405069

VL - 114

SP - 72

EP - 82

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

SN - 0022-2828

ER -

A carvedilol-responsive microRNA, miR-125b-5p protects the heart from acute myocardial infarction by repressing pro-apoptotic bak1 and klf13 in cardiomyocytes

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this