Macrophage neuronal nitric oxide synthase (NOS1) controls the inflammatory response and foam cell formation in atherosclerosis

Int Immunopharmacol. 2020 Jun:83:106382. doi: 10.1016/j.intimp.2020.106382. Epub 2020 Mar 16.

Abstract

Vascular inflammation plays a decisive role in the formation of foam cells and in the pathophysiology of atherosclerosis. However, the underlying mechanisms of these processes are not clearly understood. Macrophages engulf oxidized low-density lipoproteins (OxLDLs) via a scavenger receptor (SR), an event that mediates the elaboration of proinflammatory cytokines to initiate necrotic core formation in atherogenic plaques. In this study, we demonstrate that Nitric oxide synthase 1 (NOS1)-derived nitric oxide (NO) promotes OxLDL uptake and enhances the release of proinflammatory cytokines by macrophages. Conversely, we show that NOS1 inhibition by N(G)-nitro-L-arginine methyl ester (L-NAME) suppresses OxLDL uptake and proinflammatory cytokine expression. Current studies indicate that NOS1 plays a crucial role in vascular inflammation and in the progression of atherosclerosis. Therefore, interference with NOS1 enzymatic activity should serve as an effective strategy to reduce foam cell formation and limit the extent of atherosclerotic plaque expansion.

Keywords: Atherosclerosis; Foam cell formation; Macrophage; Neuronal nitric oxide synthase (NOS1); Oxidized low-density lipoprotein (OxLDL).

MeSH terms

  • Animals
  • Atherosclerosis / immunology*
  • Cell Differentiation
  • Cells, Cultured
  • Disease Models, Animal
  • Disease Progression
  • Foam Cells / immunology*
  • Humans
  • Inflammation / immunology*
  • Lipoproteins, LDL / metabolism
  • Macrophages / metabolism
  • Mice
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type I / antagonists & inhibitors
  • Nitric Oxide Synthase Type I / metabolism*

Substances

  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • Nitric Oxide
  • NOS1 protein, human
  • Nitric Oxide Synthase Type I
  • NG-Nitroarginine Methyl Ester