Chronic cold stress-induced myocardial injury: effects on oxidative stress, inflammation and pyroptosis.

BACKGROUND

Hypothermia is a crucial environmental factor that elevates the risk of cardiovascular disease, but the underlying effect is unclear.

OBJECTIVES

This study examined the role of cold stress (CS) in cardiac injury and its underlying mechanisms.

METHODS

In this study, a chronic CS-induced myocardial injury model was used; mice were subjected to chronic CS (4°C) for three hours per day for three weeks.

RESULTS

CS could result in myocardial injury by inducing the levels of heat shock proteins 70 (HSP70), enhancing the generation of creatine phosphokinase-isoenzyme (CKMB) and malondialdehyde (MDA), increasing the contents of tumor necrosis factor-α (TNF-α), high mobility group box 1 (HMGB1) interleukin1b (IL-1β), IL-18, IL-6, and triggering the depletion of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Multiple signaling pathways were activated by cold exposure, including pyroptosis-associated NOD-like receptor 3 (NLRP3)-regulated caspase-1-dependent/Gasdermin D (GSDMD), inflammation-related toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-mediated nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK), as well as oxidative stress-involved thioredoxin-1/thioredoxin-interacting protein (Txnip) signaling pathways, which play a pivotal role in myocardial injury resulting from hypothermia.

CONCLUSIONS

These findings provide new insights into the increased risk of cardiovascular disease at extremely low temperatures.