Research Paper Advance Articles

Caveolin-3 protects diabetic hearts from acute myocardial infarction/reperfusion injury through β2AR, cAMP/PKA, and BDNF/TrkB signaling pathways

Jiaji Gong1, , Fan Zhou1, , Simin Xie, Xin Wang1, , Junmei Xu1, , Feng Xiao1, ,

  • 1 Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha 410011, China

Received: October 22, 2019       Accepted: May 27, 2020       Published: July 21, 2020      

https://doi.org/10.18632/aging.103469
How to Cite

Copyright © 2020 Gong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Diabetes mellitus (DM) might increase the incidence and mortality of cardiac failure after acute myocardial infarction (AMI) in patients. We attempted to investigate whether Caveolin-3 showed beneficial effects in DM patient post-MI injury through the cAMP/PKA and BDNF/TrkB signaling pathways. The activity of ADRB2 and cAMP/PKA signaling were impaired in nondiabetic ischemia-reperfusion (I/R) group compared with the sham and DM groups and were more impaired in diabetic I/R group than in the I/R group. In H9C2 cells, high-glucose (HG) stimulation further enhanced H/R injury by promoting cell apoptosis, inhibiting cell viability, and suppressing TrkB and Akt signaling; in contrast, the ADRB2 agonist isoprenaline (ISO) significantly attenuated the above-described effects of HG stimulation. Caveolin-3 overexpression promoted the localization of ADRB2 on the membrane of the HG-stimulated H9C2 cells, subsequently inhibiting apoptosis and promoting cell viability. Under HG stimulation, Caveolin-3 overexpression enhanced the activity of the cAMP/PKA and BDNF/TrkB signaling pathways, whereas ADRB2 silencing reversed the effects of Caveolin-3 overexpression. In conclusion, ADRB2 agonist promoted the activity of the BDNF/TrkB and cAMP/PKA signaling pathways, mitigating the HG-aggravated H/R injuries in H9C2 cells. Caveolin-3 exerts a protective effect on diabetic hearts against I/R damage through the β2AR, cAMP/PKA, and BDNF/TrkB signaling pathways.

Abbreviations

DM: Diabetes mellitus; AMI: acute myocardial infarction; I/R: ischemia-reperfusion; HG: high-glucose; ISO: isoprenaline; BDNF: Brain-derived neurotrophic factor; OGD: oxygen-glucose deprivation; TrKB: tropomyosin-related kinase receptor B; cAMP: cyclic Adenosine monophosphate; PKA: protein kinase A; CREB: cAMP-response element binding protein; STZ: streptozotocin; ADRB2: adrenergic receptor β2; KEGG: Kyoto Encyclopedia of Genes and Genomes; LVIDs: left ventricular internal diameter end-systolic; LVIDd: Left ventricular end diastolic diameter; LVEF: Left Ventricular Ejection Fraction; LVFS: Left ventricular fraction shortening.