Essential role of caveolin-3 in adiponectin signalsome formation and adiponectin cardioprotection.

Authors

• Yajing Wang
• Xiaoliang Wang
• Jean-François Jasmin
• Wayne Bond Lau
• Rong Li
• Yuexin Yuan
• Wei Yi
• Kurt Chuprun
• Michael P Lisanti
• Walter J Koch
• Erhe Gao
• Xin-Liang Ma

Publication/Presentation Date

4-1-2012

Abstract

OBJECTIVE: Adiponectin (APN) system malfunction is causatively related to increased cardiovascular morbidity/mortality in diabetic patients. The aim of the current study was to investigate molecular mechanisms responsible for APN transmembrane signaling and cardioprotection.

METHODS AND RESULTS: Compared with wild-type mice, caveolin-3 knockout (Cav-3KO) mice exhibited modestly increased myocardial ischemia/reperfusion injury (increased infarct size, apoptosis, and poorer cardiac function recovery; P< 0.05). Although the expression level of key APN signaling molecules was normal in Cav-3KO, the cardioprotective effects of APN observed in wild-type were either markedly reduced or completely lost in Cav-3KO. Molecular and cellular experiments revealed that APN receptor 1 (AdipoR1) colocalized with Cav-3, forming AdipoR1/Cav-3 complex via specific Cav-3 scaffolding domain binding motifs. AdipoR1/Cav-3 interaction was required for APN-initiated AMP-activated protein kinase (AMPK)-dependent and AMPK-independent intracellular cardioprotective signalings. More importantly, APPL1 and adenylate cyclase, 2 immediately downstream molecules required for AMPK-dependent and AMPK-independent signaling, respectively, formed a protein complex with AdipoR1 in a Cav-3 dependent fashion. Finally, pharmacological activation of both AMPK plus protein kinase A significantly reduced myocardial infarct size and improved cardiac function in Cav-3KO animals.

CONCLUSIONS: Taken together, these results demonstrated for the first time that Cav-3 plays an essential role in APN transmembrane signaling and APN anti-ischemic/cardioprotective actions.

Volume

32

Issue

4

First Page

934

Last Page

942

ISSN

1524-4636

Published In/Presented At

Wang, Y., Wang, X., Jasmin, J. F., Lau, W. B., Li, R., Yuan, Y., Yi, W., Chuprun, K., Lisanti, M. P., Koch, W. J., Gao, E., & Ma, X. L. (2012). Essential role of caveolin-3 in adiponectin signalsome formation and adiponectin cardioprotection. Arteriosclerosis, thrombosis, and vascular biology, 32(4), 934–942. https://doi.org/10.1161/ATVBAHA.111.242164

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

22328772

Department(s)

Administration and Leadership

Document Type

Article