Targeting Adiponectin Receptor 1 Phosphorylation Against Ischemic Heart Failure.
Publication/Presentation Date
7-8-2022
Abstract
BACKGROUND: Despite significantly reduced acute myocardial infarction (MI) mortality in recent years, ischemic heart failure continues to escalate. Therapeutic interventions effectively reversing pathological remodeling are an urgent unmet medical need. We recently demonstrated that AdipoR1 (APN [adiponectin] receptor 1) phosphorylation by GRK2 (G-protein-coupled receptor kinase 2) contributes to maladaptive remodeling in the ischemic heart. The current study clarified the underlying mechanisms leading to AdipoR1 phosphorylative desensitization and investigated whether blocking AdipoR1 phosphorylation may restore its protective signaling, reversing post-MI remodeling.
METHODS: Specific sites and underlying molecular mechanisms responsible for AdipoR1 phosphorylative desensitization were investigated in vitro (neonatal and adult cardiomyocytes). The effects of AdipoR1 phosphorylation inhibition upon APN post-MI remodeling and heart failure progression were investigated in vivo.
RESULTS: Among 4 previously identified sites sensitive to GRK2 phosphorylation, alanine substitution of Ser
CONCLUSIONS: Ser
Volume
131
Issue
2
First Page
34
Last Page
34
ISSN
1524-4571
Published In/Presented At
Zhu, D., Zhang, Z., Zhao, J., Liu, D., Gan, L., Lau, W. B., Xie, D., Meng, Z., Yao, P., Tsukuda, J., Christopher, T. A., Lopez, B. L., Gao, E., Koch, W. J., Wang, Y., & Ma, X. L. (2022). Targeting Adiponectin Receptor 1 Phosphorylation Against Ischemic Heart Failure. Circulation research, 131(2), e34–e50. https://doi.org/10.1161/CIRCRESAHA.121.319976
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
35611695
Department(s)
Administration and Leadership
Document Type
Article