Rad GTPase Deletion Attenuates Post-Ischemic Cardiac Dysfunction and Remodeling
| Autor: | Brandon K. Fornwalt, Erhe Gao, Bryana R. Levitan, Christopher M. Haggerty, Jonathan Satin, Prabhakara R Nagareddy, Janet R. Manning, Catherine N. Withers, Ahmed Abdel-Latif, Lakshman Chelvarajan, Himi Tripathi, Douglas A. Andres |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | JACC: Basic to Translational Science, Vol 3, Iss 1, Pp 83-96 (2018) JACC: Basic to Translational Science |
| Popis: | Visual Abstract 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. 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. |
| Databáze: | OpenAIRE |
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