Peptidoglycan Recognition Protein 1 Attenuates Atherosclerosis by Suppressing Endothelial Cell Adhesion

J Cardiovasc Pharmacol. 2021 Oct 1;78(4):615-621. doi: 10.1097/FJC.0000000000001100.

Abstract

Peptidoglycan recognition protein 1 (PGLYRP1) has long been believed to play an important role in infectious and immune diseases. We hypothesized that it might be involved in the pathophysiology of atherosclerotic diseases, which are regarded as chronic inflammatory diseases. Serum PGLYRP1 concentrations were measured in 240 patients with coronary artery disease (CAD) and 209 age-matched and gender-matched individuals with normal coronary arteries using enzyme-linked immunosorbent assay. The expression of PGLYRP1 in atherosclerotic plaques was quantified using western blotting and immunostaining. ApoE-/- mice, fed a high-fat diet, were randomly given intraperitoneal injections of saline or recombinant PGLYRP1 protein for 12 weeks. The effects of PGLYRP1 on human umbilical vein endothelial cells were investigated by western blotting. Higher concentrations of PGLYRP1 were significantly associated with a higher risk of CAD. The odd ratio for upper quartile versus lower quartile was 2.24 (95% confidence interval: 1.21-4.13) after adjustment for sex, age, smoking, body mass index, lipid profile, blood pressure, fasting glucose, and estimated glomerular filtration rate. PGLYRP1 was highly expressed in murine atherosclerotic plaques. Recombinant PGLYRP1 protein alleviated the progress of atherosclerosis in vivo and reduced the expression of endothelial cells' adhesion molecules in vitro. In conclusion, our study suggested that PGLYRP1 is upregulated in patients with CAD and atherosclerotic plaques. PGLYRP1 may participate in the pathophysiological process of atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Biomarkers / blood
  • Case-Control Studies
  • Cell Adhesion / drug effects*
  • Cells, Cultured
  • Cytokines / blood
  • Cytokines / pharmacology*
  • Disease Models, Animal
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Male
  • Mice
  • Mice, Knockout, ApoE
  • Middle Aged
  • Recombinant Proteins / pharmacology

Substances

  • Biomarkers
  • Cytokines
  • PGLYRP1 protein, human
  • Pglyrp1 protein, mouse
  • Recombinant Proteins