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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 β1/2/3-adrenoceptors (β-AR), its downstream signaling, and inflammatory status, which play a role in cell-survival during myocardial infarction. Adult male Wistar rats were acclimated (9 °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 β1-ARs. The β2-ARs/protein kinase B/Akt were attenuated while β3-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 β1/2-AR desensitization, activation of the β3-AR/PKG/AMPK pathways, and an immunomodulatory effect.
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Details
1 Charles University, Faculty of Science, Department of Physiology, Prague 2, Czech Republic (GRID:grid.4491.8) (ISNI:0000 0004 1937 116X)
2 Czech Academy of Sciences, Institute of Animal Physiology and Genetics, Libechov, Czech Republic (GRID:grid.418095.1) (ISNI:0000 0001 1015 3316)
3 Charles University, First Faculty of Medicine, Center for Advanced Preclinical Imaging (CAPI), Prague, Czech Republic (GRID:grid.4491.8) (ISNI:0000 0004 1937 116X)
4 Slovak Academy of Sciences, Centre of Experimental Medicine, Institute for Heart Research, Bratislava, Slovak Republic (GRID:grid.419303.c) (ISNI:0000 0001 2180 9405)
5 Charles University, Faculty of Science, Department of Physiology, Prague 2, Czech Republic (GRID:grid.4491.8) (ISNI:0000 0004 1937 116X); Czech Academy of Sciences, Institute of Biotechnology, Prague-West, Czech Republic (GRID:grid.418095.1) (ISNI:0000 0001 1015 3316); Griffith University, School of Pharmacy and Medical Science, Southport, Australia (GRID:grid.1022.1) (ISNI:0000 0004 0437 5432)
6 Czech Academy of Sciences, Institute of Physiology, Prague, Czech Republic (GRID:grid.418095.1) (ISNI:0000 0001 1015 3316)
7 Charles University, Faculty of Science, Department of Physiology, Prague 2, Czech Republic (GRID:grid.4491.8) (ISNI:0000 0004 1937 116X); Czech Academy of Sciences, Institute of Physiology, Prague, Czech Republic (GRID:grid.418095.1) (ISNI:0000 0001 1015 3316)