Rad GTPase Deletion Attenuates Post-Ischemic Cardiac Dysfunction and Remodeling

Janet R. Manning; Lakshman Chelvarajan; Bryana M. Levitan; Catherine N. Withers; Prabhakara R. Nagareddy; Christopher M. Haggerty; Brandon K. Fornwalt; Erhe Gao; Himi Tripathi; Ahmed Abdel-Latif; Douglas A. Andres; Jonathan Satin

doi:10.1016/j.jacbts.2017.09.004

Rad GTPase Deletion Attenuates Post-Ischemic Cardiac Dysfunction and Remodeling

Janet R. Manning, Lakshman Chelvarajan, Bryana M. Levitan, Catherine N. Withers, Prabhakara R. Nagareddy, Christopher M. Haggerty, Brandon K. Fornwalt, Erhe Gao, Himi Tripathi, Ahmed Abdel-Latif, Douglas A. Andres, Jonathan Satin

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

2 Scopus citations

Abstract

The protein Rad interacts with the L-type calcium channel complex to modulate trigger Ca²⁺ and hence to govern contractility. Reducing Rad levels increases cardiac output. Ablation of Rad also attenuated the inflammatory response following acute myocardial infarction. Future studies to target deletion of Rad in the heart could be conducted to establish a novel treatment paradigm whereby pathologically stressed hearts would be given safe, stable positive inotropic support without arrhythmias and without pathological structural remodeling. Future investigations will also focus on establishing inhibitors of Rad and testing the efficacy of Rad deletion in cardioprotection relative to the time of onset of acute myocardial infarction.

Original language	English
Pages (from-to)	83-96
Number of pages	14
Journal	JACC: Basic to Translational Science
Volume	3
Issue number	1
DOIs	https://doi.org/10.1016/j.jacbts.2017.09.004
State	Published - Feb 2018

Bibliographical note

Funding Information:
Dr. Manning has received grants from the American Heart Association (14POST20460224) and the NIH (F32HL126300). Dr. Withers has received an NIH grant (T32-HL0727423) and an NSF grant (DGE-1247392). Dr. Nagareddy has received an NIH grant (R00 HL22505). Dr. Abdel-Latif has received NIH grants (UK Cobre NIH P20 GM 103527 and NIH R56 HL124266). Drs. Withers and Andres has received the IDeA award 8 P20 GM103527. Drs. Andres and Satin have received grants from the NIH (R56HL131782) and the American Heart Association (GRNT27790094). Dr. Andres has received a UK Research Professorship. Dr. Satin has received an NIH grant (R01 HL074091). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright:
© 2018 The Authors

Keywords

calcium channel
cardioprotection
inflammation
myocardial infarction

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jacbts.2017.09.004

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title = "Rad GTPase Deletion Attenuates Post-Ischemic Cardiac Dysfunction and Remodeling",

abstract = "The protein Rad interacts with the L-type calcium channel complex to modulate trigger Ca2+ and hence to govern contractility. Reducing Rad levels increases cardiac output. Ablation of Rad also attenuated the inflammatory response following acute myocardial infarction. Future studies to target deletion of Rad in the heart could be conducted to establish a novel treatment paradigm whereby pathologically stressed hearts would be given safe, stable positive inotropic support without arrhythmias and without pathological structural remodeling. Future investigations will also focus on establishing inhibitors of Rad and testing the efficacy of Rad deletion in cardioprotection relative to the time of onset of acute myocardial infarction.",

keywords = "calcium channel, cardioprotection, inflammation, myocardial infarction",

author = "Manning, {Janet R.} and Lakshman Chelvarajan and Levitan, {Bryana M.} and Withers, {Catherine N.} and Nagareddy, {Prabhakara R.} and Haggerty, {Christopher M.} and Fornwalt, {Brandon K.} and Erhe Gao and Himi Tripathi and Ahmed Abdel-Latif and Andres, {Douglas A.} and Jonathan Satin",

note = "Funding Information: Dr. Manning has received grants from the American Heart Association (14POST20460224) and the NIH (F32HL126300). Dr. Withers has received an NIH grant (T32-HL0727423) and an NSF grant (DGE-1247392). Dr. Nagareddy has received an NIH grant (R00 HL22505). Dr. Abdel-Latif has received NIH grants (UK Cobre NIH P20 GM 103527 and NIH R56 HL124266). Drs. Withers and Andres has received the IDeA award 8 P20 GM103527. Drs. Andres and Satin have received grants from the NIH (R56HL131782) and the American Heart Association (GRNT27790094). Dr. Andres has received a UK Research Professorship. Dr. Satin has received an NIH grant (R01 HL074091). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2018 The Authors",

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AU - Nagareddy, Prabhakara R.

AU - Haggerty, Christopher M.

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AU - Gao, Erhe

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AU - Abdel-Latif, Ahmed

AU - Andres, Douglas A.

AU - Satin, Jonathan

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AB - The protein Rad interacts with the L-type calcium channel complex to modulate trigger Ca2+ and hence to govern contractility. Reducing Rad levels increases cardiac output. Ablation of Rad also attenuated the inflammatory response following acute myocardial infarction. Future studies to target deletion of Rad in the heart could be conducted to establish a novel treatment paradigm whereby pathologically stressed hearts would be given safe, stable positive inotropic support without arrhythmias and without pathological structural remodeling. Future investigations will also focus on establishing inhibitors of Rad and testing the efficacy of Rad deletion in cardioprotection relative to the time of onset of acute myocardial infarction.

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Rad GTPase Deletion Attenuates Post-Ischemic Cardiac Dysfunction and Remodeling

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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