Cold acclimation preserved cardiac function under extreme cold stress via brown adipose tissue-derived extracellular vesicles enriched with lncRNA Morrbid, which mitigates cardiomyocyte apoptosis.
Does cold acclimation protect against extreme cold-induced myocardial injury via BAT-derived extracellular vesicles in mice?
Cold acclimation confers remote cardioprotection against extreme cold via a BAT-Heart axis involving EV-mediated transfer of lncRNA Morrbid.
Background Extreme cold causes myocardial injury; however, cold acclimation (CA) enhances myocardial tolerance. This study investigated whether brown adipose tissue (BAT)-derived extracellular vesicles (BAT-EVs) contribute to CA-induced cardioprotection. Methods Mice were subjected to CA or acute cold stress. Cardiac function was assessed using echocardiography and biomarkers. Interscapular BAT (iBAT) ablation has confirmed the necessity of iBAT. EVs were characterized and tested in HL-1 cardiomyocytes. Transcriptomics and specific gene knockdowns have identified key molecular mechanisms. Results CA preserved cardiac function and integrity under -25 °C stress, and these effects were abolished by iBAT ablation. EVs from CA mice mediate this protection by mitigating cardiomyocyte apoptosis. Mechanistically, lncRNA Morrbid was enriched in iBAT and serum EVs after CA. iBAT-specific Morrbid knockdown significantly attenuates EV-mediated protection. Furthermore, Morrbid was associated with upregulation of Serpine1 in cardiomyocytes; silencing Serpine1 abolished anti-apoptotic benefits. Conclusion This study identified a BAT-Heart axis where CA stimulates the release of Morrbid-enriched EVs. These vesicles serve as an important mechanism to confer remote cardioprotection, potentially by upregulating cardiac Serpine1 and suppressing apoptosis, highlighting a potential therapeutic strategy for cold-induced injury.
Zhang et al. (Mon,) conducted a other in Cold-induced myocardial injury. Cold acclimation (CA) and BAT-derived extracellular vesicles vs. Acute cold stress or iBAT ablation was evaluated on Cardiac function and integrity under -25 °C stress. Cold acclimation preserved cardiac function under extreme cold stress via brown adipose tissue-derived extracellular vesicles enriched with lncRNA Morrbid, which mitigates cardiomyocyte apoptosis.