Persistent cold exposure accelerated atherosclerotic plaque growth and instability in ApoE(-/-) and Ldlr(-/-) mice via UCP1-dependent lipolysis.
Does persistent cold exposure accelerate atherosclerotic plaque growth and instability in ApoE(-/-) and Ldlr(-/-) mice?
Cold exposure accelerates atherosclerosis in mice via UCP1-dependent lipolysis and reduced adiponectin, providing a mechanistic explanation for cold-associated cardiovascular risk.
Molecular mechanisms underlying the cold-associated high cardiovascular risk remain unknown. Here, we show that the cold-triggered food-intake-independent lipolysis significantly increased plasma levels of small low-density lipoprotein (LDL) remnants, leading to accelerated development of atherosclerotic lesions in mice. In two genetic mouse knockout models (apolipoprotein E(-/-) ApoE(-/-) and LDL receptor(-/-) Ldlr(-/-) mice), persistent cold exposure stimulated atherosclerotic plaque growth by increasing lipid deposition. Furthermore, marked increase of inflammatory cells and plaque-associated microvessels were detected in the cold-acclimated ApoE(-/-) and Ldlr(-/-) mice, leading to plaque instability. Deletion of uncoupling protein 1 (UCP1), a key mitochondrial protein involved in thermogenesis in brown adipose tissue (BAT), in the ApoE(-/-) strain completely protected mice from the cold-induced atherosclerotic lesions. Cold acclimation markedly reduced plasma levels of adiponectin, and systemic delivery of adiponectin protected ApoE(-/-) mice from plaque development. These findings provide mechanistic insights on low-temperature-associated cardiovascular risks.
Dong et al. (Mon,) conducted a other in Atherosclerosis. Cold exposure was evaluated on Atherosclerotic plaque growth and instability. Persistent cold exposure accelerated atherosclerotic plaque growth and instability in ApoE(-/-) and Ldlr(-/-) mice via UCP1-dependent lipolysis.