Continuous short-term acclimation to moderate cold elicits cardioprotection in rats, and alters β-adrenergic signaling and immune status
Abstract
Moderate cold acclimation (MCA) is a non-invasive intervention mitigating effects of various pathological conditions including myocardial infarction. We aim to determine the shortest cardioprotective regimen of MCA and the response of beta 1/2/3-adrenoceptors (beta-AR), its downstream signaling, and inflammatory status, which play a role in cell-survival during myocardial infarction.
Adult male Wistar rats were acclimated (9 degrees C, 1-3-10 days). Infarct size, echocardiography, western blotting, ELISA, mitochondrial respirometry, receptor binding assay, and quantitative immunofluorescence microscopy were carried out on left ventricular myocardium and brown adipose tissue (BAT).
MultiPlex analysis of cytokines and chemokines in serum was accomplished. We found that short-term MCA reduced myocardial infarction, improved resistance of mitochondria to Ca2+-overload, and downregulated beta 1-ARs.
The beta 2-ARs/protein kinase B/Akt were attenuated while beta 3-ARs translocated on the T-tubular system suggesting its activation. Protein kinase G (PKG) translocated to sarcoplasmic reticulum and phosphorylation of AMPKThr172 increased after 10 days.
Principal component analysis revealed a significant shift in cytokine/chemokine serum levels on day 10 of acclimation, which corresponds to maturation of BAT. In conclusion, short-term MCA increases heart resilience to ischemia without any negative side effects such as hypertension or hypertrophy.
Cold-elicited cardioprotection is accompanied by beta 1/2-AR desensitization, activation of the beta 3-AR/PKG/AMPK pathways, and an immunomodulatory effect.