Research Paper Volume 12, Issue 14 pp 14300—14313
Caveolin-3 protects diabetic hearts from acute myocardial infarction/reperfusion injury through β2AR, cAMP/PKA, and BDNF/TrkB signaling pathways
- 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.103469How to Cite
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.