Cardiac Gene Therapy With Relaxin Receptor 1 Overexpression Protects Against Acute Myocardial Infarction
- Resource Type
- Authors
- Teja Devarakonda; Adolfo G. Mauro; Chad Cain; Anindita Das; Fadi N. Salloum
- Source
- JACC: Basic to Translational Science
- Subject
- LV function
RXFP1
mRNA, messenger ribonucleic acid
ischemia-reperfusion injury
eNOS, endothelial nitric oxide synthase
RXFP1, relaxin family peptide receptor 1
SIRO, simulated ischemia and reoxygenation
CMV, cytomegalovirus
gene therapy
PV, pressure-volume
AAV, adeno-associated virus
VEC, empty vector
GLS, global longitudinal strain
MI, myocardial infarction
IR, ischemia-reperfusion
Preclinical Research
Cardiology and Cardiovascular Medicine
relaxin
LV, left ventricular
MAPK, mitogen-activated protein kinase
- Language
- ISSN
- 2452-302X
Visual Abstract
Highlights • AAV9 vectors can upregulate Rxfp1 mRNA in murine heart after intravenous injection. • RXFP1 upregulation sensitizes the left ventricle to relaxin-induced inotropy. • RXFP1 overexpression protects heart from ischemia-reperfusion injury.
Summary Relaxin is a pleiotropic hormone shown to confer cardioprotection in several preclinical models of cardiac ischemia-reperfusion injury. In the present study, the effects of up-regulating relaxin family peptide receptor 1 (RXFP1) via adeno-associated virus serotype 9 (AAV9) vectors were investigated in a mouse model of myocardial infarction. AAV9-RXFP1 vectors were generated and injected in adult male CD1 mice. Up-regulation of Rxfp1 was confirmed via quantitative polymerase chain reaction, and overexpressing animals showed increased sensitivity to relaxin-induced ventricular inotropic response. Overexpressing animals also demonstrated reduced infarct size and preserved cardiac function 24 hours after ischemia-reperfusion. Up-regulation of RXFP1 via AAV9 vectors has potential therapeutic utility in preventing adverse remodeling after myocardial infarction.