Inflammatory Macrophage Interleukin-1ß Mediates High-Fat Diet-Induced Heart Failure With Preserved Ejection Fraction.
JACC Basic Transl Sci
; 8(2): 174-185, 2023 Feb.
Article
in En
| MEDLINE
| ID: mdl-36908663
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)-1ß levels, and proinflammatory cardiac macrophage accumulation. DD was significantly ameliorated by suppressing IL-1ß signaling or depleting macrophages. Mice with macrophages unable to adopt a proinflammatory phenotype were low in cardiac IL-1ß levels and were resistant to HFD-induced DD. IL-1ß 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-1ß and mitoROS production.
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-1ß; 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
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Risk_factors_studies
Language:
En
Journal:
JACC Basic Transl Sci
Year:
2023
Document type:
Article
Affiliation country:
United States