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Updated: Aug 6, 2026
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Heat shock protein 72 attenuates atherosclerosis in apolipoprotein E-deficient mice
Rintaro Yoshizumi1, Tatsuya Kondo2,3, Takuro Watanabe1
1Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Kumamoto, Japan.
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.
