NOS1-mediated macrophage and endothelial cell interaction in the progression of atherosclerosis

Cell Biol Int. 2021 Jun;45(6):1191-1201. doi: 10.1002/cbin.11558. Epub 2021 Feb 4.

Abstract

Atherosclerosis is a chronic inflammatory disease arising due to an imbalance in lipid metabolism and maladaptive immune response driven by the accumulation of cholesterol-laden macrophages in the artery wall. Interactions between monocytes/macrophages and endothelial cells play an essential role in the pathogenesis of atherosclerosis. In our current study, nitric oxide synthase 1 (NOS1)-derived nitric oxide (NO) has been identified as a regulator of macrophage and endothelial cell interaction. Oxidized LDL (OxLDL) activates NOS1, which results in the expression of CD40 ligand in macrophages. OxLDL-stimulated macrophages produce some soluble factors which increase the CD40 receptor expression in endothelial cells. This increases the interaction between the macrophages and endothelial cells, which leads to an increase in the inflammatory response. Inhibition of NOS1-derived NO might serve as an effective strategy to reduce foam cell formation and limit the extent of atherosclerotic plaque expansion.

Keywords: CD40/CD40L; atherosclerosis; cardiovascular disease; macrophage; neuronal nitric oxide synthase (NOS1); oxidized low-density lipoprotein.

MeSH terms

  • Animals
  • Atherosclerosis* / metabolism
  • Atherosclerosis* / pathology
  • CD40 Antigens / metabolism
  • Cell Communication
  • Endothelial Cells* / metabolism
  • Endothelial Cells* / pathology
  • Humans
  • Lipoproteins, LDL / metabolism
  • Macrophages* / metabolism
  • Macrophages* / pathology
  • Mice
  • Nitric Oxide Synthase Type I / metabolism*
  • THP-1 Cells

Substances

  • CD40 Antigens
  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • NOS1 protein, human
  • Nitric Oxide Synthase Type I