PMID- 34954523 OWN - NLM STAT- MEDLINE DCOM- 20220208 LR - 20240226 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 588 DP - 2022 Jan 15 TI - Abnormal histidine metabolism promotes macrophage lipid accumulation under Ox-LDL condition. PG - 161-167 LID - S0006-291X(21)01703-4 [pii] LID - 10.1016/j.bbrc.2021.12.069 [doi] AB - Distinct macrophage populations exert highly heterogeneity and perform various functions, among which, a crucial function of lipid metabolism is highlighted. However, the role of histidine metabolism disorder in macrophage lipid metabolism remains elusive. Addressed this question, we sorted and cultured the bone marrow-derived macrophages (BMDMs) of histidine decarboxylase (Hdc) knockout (Hdc(-/-)) mice with an in vitro oxidized low-density lipoprotein (ox-LDL) model, and detected the intracellular lipids by Oil Red O staining as well as lipid probe staining. Astemizole, a canonical and long-acting histamine H(1) receptor (H(1)R) antagonist, was applied to elucidate the impact of antagonizing the H(1)R-dependent signaling pathway on macrophage lipid metabolism. Subsequently, the differential expressed genes were screened and analyzed in the bone marrow-derived CD11b(+) immature myeloid cells of Hdc(-/-) and Hdc(+/+) mice with a high fat diet by the microarray study. The expression levels of cholesterol metabolism-related genes were examined by qRT-PCR to explore underlying mechanisms. Lastly, we used a high-sensitivity histidine probe to detect the intracellular histidine in the BMDMs after oxidative stress. The results revealed that histidine metabolism disorder and histamine deficiency aggravated lipid accumulation in the ox-LDL-treated BMDMs. The expression level of H(1)R gene in the BMDMs was down-regulated after ox-LDL stimulation. The disruption of the H(1)R-dependent signaling pathway by astemizole further exacerbated ox-LDL-induced lipid deposition in the BMDMs partly by up-regulating scavenger receptor class A (SR-A) for lipid intake, down-regulating neutral cholesteryl ester hydrolase (nCEH) for cholesterol esterification and down-regulating ATP-binding cassette transporters A1 (ABCA1) and ABCG1 for reverse cholesterol transport. The intracellular histidine increased under ox-LDL condition, which was further increased by Hdc knockout. Collectively, these results partially reveal the relationship between histidine metabolism and lipid metabolism in the BMDMs and offer a novel strategy for lipid metabolism disorder-associated diseases. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Zhu, Baoling AU - Zhu B AD - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. FAU - Zhang, Zhiwei AU - Zhang Z AD - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; Reproductive Medicine Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. FAU - Wang, Xiangfei AU - Wang X AD - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. FAU - Zhang, Weiwei AU - Zhang W AD - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China. FAU - Shi, Hongyu AU - Shi H AD - Department of Cardiology, Wusong Hospital of Zhongshan Hospital, Fudan University, Shanghai, 200940, China. FAU - Song, Zhifeng AU - Song Z AD - Department of Oral Mucosa and Periodontitis, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200433, China. FAU - Ding, Suling AU - Ding S AD - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China. Electronic address: dingsuling1984@163.com. FAU - Yang, Xiangdong AU - Yang X AD - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China; Department of Cardiology, Wusong Hospital of Zhongshan Hospital, Fudan University, Shanghai, 200940, China. Electronic address: yangxiangdong_zs@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211220 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Lipoproteins, LDL) RN - 0 (Receptors, Histamine) RN - 0 (oxidized low density lipoprotein) RN - 4QD397987E (Histidine) RN - 820484N8I3 (Histamine) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - Cholesterol/metabolism MH - Gene Expression Profiling MH - Gene Expression Regulation/drug effects MH - Histamine/deficiency MH - Histidine/*metabolism MH - *Lipid Metabolism/drug effects/genetics MH - Lipoproteins, LDL/*pharmacology MH - Macrophages/drug effects/*metabolism MH - Male MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Receptors, Histamine/metabolism MH - Signal Transduction/drug effects MH - Mice OTO - NOTNLM OT - Histamine H1 receptor OT - Histidine decarboxylase OT - Histidine metabolism OT - Lipid metabolism OT - Macrophage COIS- Declaration of competing interest The authors declare no conflict of interest. EDAT- 2021/12/27 06:00 MHDA- 2022/02/09 06:00 CRDT- 2021/12/26 20:50 PHST- 2021/10/26 00:00 [received] PHST- 2021/12/17 00:00 [revised] PHST- 2021/12/18 00:00 [accepted] PHST- 2021/12/27 06:00 [pubmed] PHST- 2022/02/09 06:00 [medline] PHST- 2021/12/26 20:50 [entrez] AID - S0006-291X(21)01703-4 [pii] AID - 10.1016/j.bbrc.2021.12.069 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2022 Jan 15;588:161-167. doi: 10.1016/j.bbrc.2021.12.069. Epub 2021 Dec 20.