2. Academic Validation
  3. Blocking H1R signal aggravates atherosclerosis by promoting inflammation and foam cell formation

Blocking H1R signal aggravates atherosclerosis by promoting inflammation and foam cell formation

  • J Mol Med (Berl). 2024 May 11. doi: 10.1007/s00109-024-02453-5.
Baoling Zhu # 1 2,  Yi Yang # 3,  Xiangfei Wang # 4,  Dili Sun # 4,  Xiyang Yang 4,  Xiaowei Zhu 4 5,  Suling Ding 1,  Chun Xiao 6,  Yunzeng Zou 7 8,  Xiangdong Yang 9 10 11 12
Affiliations

Affiliations

  • 1 Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
  • 2 School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Shandong, 266071, China.
  • 3 Department of Medical Laboratory, College of Medical Technology, Shanghai University of Medicine & Health Sciences, Shanghai, 201318, China.
  • 4 Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 5 Department of Cardiology, Zhongshan Hospital Wusong Branch, Fudan University Shanghai, Shanghai, 200940, China.
  • 6 Department of Cardiology, Third People's Hospital of Huizhou, Guangdong, 516003, China. huizhouxiaoc@163.com.
  • 7 Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China. zou.yunzeng@zs-hospital.sh.cn.
  • 8 Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. zou.yunzeng@zs-hospital.sh.cn.
  • 9 Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China. yangxiangdong_zs@163.com.
  • 10 Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. yangxiangdong_zs@163.com.
  • 11 Department of Cardiology, Zhongshan Hospital Wusong Branch, Fudan University Shanghai, Shanghai, 200940, China. yangxiangdong_zs@163.com.
  • 12 Department of Cardiology, Third People's Hospital of Huizhou, Guangdong, 516003, China. yangxiangdong_zs@163.com.
  • # Contributed equally.
PMID: 38733386 DOI: 10.1007/s00109-024-02453-5
Abstract

Atherosclerosis (AS) is a chronic inflammatory arterial disease, in which abnormal lipid metabolism and foam cell formation play key roles. Histamine is a vital biogenic amine catalyzed by histidine decarboxylase (HDC) from L-histidine. Histamine H1 receptor (H1R) antagonist is a commonly encountered anti-allergic agent in the clinic. However, the role and mechanism of H1R in atherosclerosis have not been fully elucidated. Here, we explored the effect of H1R on atherosclerosis using Apolipoprotein E-knockout (apoE-/-) mice with astemizole (AST, a long-acting H1R antagonist) treatment. The results showed that AST increased atherosclerotic plaque area and hepatic lipid accumulation in mice. The result of microarray study identified a significant change of endothelial Lipase (LIPG) in CD11b+ myeloid cells derived from HDC-knockout (HDC-/-) mice compared to WT mice. Blocking H1R promoted the formation of foam cells from bone marrow-derived macrophages (BMDMs) of mice by up-regulating p38 mitogen-activated protein kinase (p38 MAPK) and LIPG signaling pathway. Taken together, these findings demonstrate that blocking H1R signal aggravates atherosclerosis by promoting abnormal lipid metabolism and macrophage-derived foam cell formation via p38 MAPK-LIPG signaling pathway. KEY MESSAGES: Blocking H1R signal with AST aggravated atherosclerosis and increased hepatic lipid accumulation in high-fat diet (HFD)-fed apoE-/- mice. Blocking H1R signal promoted macrophage-derived foam cell formation via p38 MAPK-LIPG signaling pathway.

Keywords

Atherosclerosis; H1R; LIPG; Macrophage-derived foam cell formation; P38 MAPK.

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