Inflammatory Macrophage Interleukin-1β Mediates High-Fat Diet-Induced Heart Failure With Preserved Ejection Fraction

Hong Liu; Yimao Huang; Yang Zhao; Gyeoung-Jin Kang; Feng Feng; Xiaodan Wang; Man Liu; Guangbin Shi; Xavier Revelo; David Bernlohr; Samuel C Dudley Jr

doi:10.1016/j.jacbts.2022.08.003

Inflammatory Macrophage Interleukin-1β Mediates High-Fat Diet-Induced Heart Failure With Preserved Ejection Fraction

JACC Basic Transl Sci. 2022 Nov 30;8(2):174-185. doi: 10.1016/j.jacbts.2022.08.003. eCollection 2023 Feb.

Authors

Affiliations

¹ Division of Cardiology, Department of Medicine, the Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota, USA.
² Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
³ Division of Cardiology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, Gansu, China.
⁴ Division of Cardiology, Cardiovascular Research Center, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
⁵ Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, Minnesota, USA.

Abstract

Diabetes mellitus (DM) is a main risk factor for diastolic dysfunction (DD) and heart failure with preserved ejection fraction. High-fat diet (HFD) mice presented with diabetes mellitus, DD, higher cardiac interleukin (IL)-1β levels, and proinflammatory cardiac macrophage accumulation. DD was significantly ameliorated by suppressing IL-1β signaling or depleting macrophages. Mice with macrophages unable to adopt a proinflammatory phenotype were low in cardiac IL-1β levels and were resistant to HFD-induced DD. IL-1β enhanced mitochondrial reactive oxygen species (mitoROS) in cardiomyocytes, and scavenging mitoROS improved HFD-induced DD. In conclusion, macrophage-mediated inflammation contributed to HFD-associated DD through IL-1β and mitoROS production.

Keywords: CCR2, C-C motif chemokine receptor 2; CM, cardiomyocyte; DD, diastolic dysfunction; DM, diabetes mellitus; EF, ejection fraction; FABP4, fatty acid binding protein 4; HF, heart failure; HFD, high-fat diet; HFpEF; HFpEF, heart failure with preserved ejection fraction; IL, interleukin; IL-1β; IL1RA, interleukin 1 receptor antagonist; KO, knockout; MCP, monocyte chemoattractant protein; MyBP-C, myosin binding protein C; TGF, transforming growth factor; TNF, tumor necrosis factor; Timd4, T cell immunoglobulin and mucin domain containing 4; WT, wild-type; diabetes; diastolic dysfunction; inflammation; macrophage; mitoROS, mitochondrial reactive oxygen species; mitochondria.

Grants and funding

R01 HL155993/HL/NHLBI NIH HHS/United States