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Rad GTPase Deletion Attenuates Post-Ischemic Cardiac Dysfunction and Remodeling
- Source :
- JACC: Basic to Translational Science, Vol 3, Iss 1, Pp 83-96 (2018), JACC: Basic to Translational Science
- Publication Year :
- 2018
- Publisher :
- Elsevier, 2018.
-
Abstract
- Visual Abstract<br />Highlights • Rad-GTPase is an LTCC component that functions to govern calcium current in the myocardium. • Deletion of Rad increases myocardial contractility secondary to increased trigger calcium entry. • AMI induces heart failure, including reduced calcium homeostasis, but deletion of Rad prevents AMI myocardial calcium alterations. • Rad deletion prevents post-MI scar spread by attenuating the inflammatory response. • Future studies will explore whether Rad deletion is an effective therapeutic direction for providing combined safe, stable inotropic support to the failing heart in concert with protection against inflammatory signaling.<br />Summary 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.
- Subjects :
- 0301 basic medicine
Inotrope
medicine.medical_specialty
Cardiac output
lcsh:Diseases of the circulatory (Cardiovascular) system
Inflammation
GTPase
030204 cardiovascular system & hematology
Contractility
PRECLINICAL RESEARCH
03 medical and health sciences
PCR, polymerase chain reaction
0302 clinical medicine
GTPase, guanosine triphosphatase
Internal medicine
medicine
EF, ejection fraction
Myocardial infarction
HFrEF, heart failure with reduced ejection fraction
Cardioprotection
business.industry
Calcium channel
medicine.disease
WT, wild-type
LTCC, L-type calcium channel complex
eye diseases
AMI, acute myocardial infarction
LAD, left anterior descending coronary artery
030104 developmental biology
myocardial infarction
inflammation
lcsh:RC666-701
cardioprotection
MI, myocardial infarction
RNA, ribonucleic acid
Cardiology
calcium channel
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Subjects
Details
- Language :
- English
- Volume :
- 3
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- JACC: Basic to Translational Science
- Accession number :
- edsair.doi.dedup.....2afb07219af2b9f2bb17a928ba4255c1