High-Fat Diet Enhances Neutrophil Adhesion in LDLR-Null Mice Via Hypercitrullination of Histone H3

JACC Basic Transl Sci. 2021 May 19;6(6):507-523. doi: 10.1016/j.jacbts.2021.04.002. eCollection 2021 Jun.

Abstract

Neutrophil adhesion on the atheroprone femoral artery of high-fat diet-fed low-density lipoprotein receptor-null mice was enhanced more than in wild-type mice. The inhibition of histone H3 citrullination of neutrophils reversed the enhancement of neutrophil adhesion, suggesting that hypercitrullination contributes to enhanced neutrophil adhesion. Furthermore, pemafibrate reduced the citrullination of histone H3 in these mice. Therefore, the hypercitrullination of histone H3 in neutrophils contributes to atherosclerotic vascular inflammation.

Keywords: BM, bone marrow; BW, body weight; DNaseI, deoxyribonuclease I; GM-CSF, granulocyte-macrophage colony-stimulating factor; HFD, high-fat diet; HUVECs, human umbilical vein endothelial cells; IVM, intravital microscopy; LDLR, low-density lipoprotein receptor; LysM, lysosome M; MPO, myeloperoxidase; NC, normal chow; NE, neutrophil elastase; NET, neutrophil extracellular trap; PAD4, peptidylarginine deiminase 4; PPAR, peroxisome proliferator-activated receptor; TC, total cholesterol; TDFA, N-acetyl-l-threonyl-l-α-aspartyl-N5-(2-fluoro-1-iminoethyl)-l-ornithinamide trifluoroacetate salt; TG, triglyceride; citrullination; cxcl1; eGFP, enhanced green fluorescent protein; in vivo imaging; neutrophil; vascular inflammation; wt, wild type.