Heat shock protein 72 attenuates atherosclerosis in apolipoprotein E‐deficient mice

Background Heat shock (HS) and mild electrical stimulation (MES) induce the expression of heat shock protein 72 (HSP72), which suppresses endoplasmic reticulum stress, oxidative stress, and c‐Jun N‐terminal kinase (JNK) activity, thereby ameliorating pathophysiologic abnormalities associated with diabetes. Aims This study aims to investigate whether HS + MES influences the development of atherosclerosis. Methods HSP72 +/+ /ApoE −/− and HSP72 −/− /ApoE −/− mice were fed a high‐fat diet and treated with either sham or HS + MES. Atherosclerotic lesion formation and oxidative stress were evaluated histologically, while HSP72 expression, macrophage markers, and proinflammatory mediators were analyzed in bone marrow‐derived macrophages (BMMs). Results In HSP72 +/+ /ApoE −/− mice, HS + MES reduced atherosclerotic lesion size and necrotic core formation, whereas these effects were absent in HSP72 −/− /ApoE −/− mice. Plaque immunostaining revealed significantly lower 4‐hydroxynonenal and F4/80 levels in HS + MES‐treated HSP72 +/+ /ApoE −/− mice. In vitro , HS + MES increased HSP72 mRNA in BMMs, suppressed lipopolysaccharide‐induced monocyte chemotactic protein‐1 (MCP‐1) and inducible nitric oxide synthase (iNOS) expression, inhibited JNK phosphorylation, and promoted macrophage polarization from M1 to M2. Conclusions Collectively, these findings indicate that induction of HSP72 expression by HS + MES prevents atherogenesis independently of glucose homeostasis.