Rad GTPase Deletion Atenuates Post-Ischemic Cardiac Dysfunction and Remodeling

Authors

Janet R. Manning, University of KentuckyFollow
Lakshman Chelvarajan, University of KentuckyFollow
Bryana R. Levitan, University of KentuckyFollow
Catherine Nicole Kaminski Withers, University of KentuckyFollow
Prabhakara R. Nagareddy, The University of Alabama at Birmingham
Christopher M. Haggerty, University of KentuckyFollow
Brandon K. Fornwalt, University of KentuckyFollow
Erhe Gao, Temple University
Himi Tripathi, University of KentuckyFollow
Ahmed Abdel-Latif, University of KentuckyFollow
Douglas A. Andres, University of KentuckyFollow
Jonathan Satin, University of KentuckyFollow

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.

Document Type

Article

Publication Date

2-2018

Notes/Citation Information

Published in JACC: Basic to Translational Science, v. 3, no. 1, p. 83-96.

© 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.jacbts.2017.09.004

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).

Repository Citation

Manning, Janet R.; Chelvarajan, Lakshman; Levitan, Bryana R.; Withers, Catherine Nicole Kaminski; Nagareddy, Prabhakara R.; Haggerty, Christopher M.; Fornwalt, Brandon K.; Gao, Erhe; Tripathi, Himi; Abdel-Latif, Ahmed; Andres, Douglas A.; and Satin, Jonathan, "Rad GTPase Deletion Atenuates Post-Ischemic Cardiac Dysfunction and Remodeling" (2018). Physiology Faculty Publications. 125.
https://uknowledge.uky.edu/physiology_facpub/125