Role of the Scavenger Receptor CD36 in Accelerated Diabetic Atherosclerosis

Int J Mol Sci. 2020 Oct 5;21(19):7360. doi: 10.3390/ijms21197360.

Abstract

Diabetes mellitus entails increased atherosclerotic burden and medial arterial calcification, but the precise mechanisms are not fully elucidated. We aimed to investigate the implication of CD36 in inflammation and calcification processes orchestrated by vascular smooth muscle cells (VSMCs) under hyperglycemic and atherogenic conditions. We examined the expression of CD36, pro-inflammatory cytokines, endoplasmic reticulum (ER) stress markers, and mineralization-regulating enzymes by RT-PCR in human VSMCs, cultured in a medium containing normal (5 mM) or high glucose (22 mM) for 72 h with or without oxidized low-density lipoprotein (oxLDL) (24 h). The uptake of 1,1'-dioctadecyl-3,3,3',3-tetramethylindocarbocyanine perchlorate-fluorescently (DiI) labeled oxLDL was quantified by flow cytometry and fluorimetry and calcification assays were performed in VSMC cultured in osteogenic medium and stained by alizarin red. We observed induction in the expression of CD36, cytokines, calcification markers, and ER stress markers under high glucose that was exacerbated by oxLDL. These results were confirmed in carotid plaques from subjects with diabetes versus non-diabetic subjects. Accordingly, the uptake of DiI-labeled oxLDL was increased after exposure to high glucose. The silencing of CD36 reduced the induction of CD36 and the expression of calcification enzymes and mineralization of VSMC. Our results indicate that CD36 signaling is partially involved in hyperglycemia and oxLDL-induced vascular calcification in diabetes.

Keywords: atherosclerosis; diabetes; inflammation; scavenger receptor CD36; vascular calcification.

MeSH terms

  • Aged
  • Atherosclerosis / genetics*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • CD36 Antigens / genetics*
  • CD36 Antigens / metabolism
  • Calcinosis / genetics*
  • Calcinosis / metabolism
  • Calcinosis / pathology
  • Diabetes Complications / genetics*
  • Diabetes Complications / metabolism
  • Diabetes Complications / pathology
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology
  • Female
  • Flow Cytometry
  • Glucose / adverse effects
  • Humans
  • Hyperglycemia / genetics
  • Hyperglycemia / metabolism
  • Hyperglycemia / pathology
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Lipoproteins, LDL / genetics
  • Lipoproteins, LDL / metabolism
  • Male
  • Middle Aged
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology
  • Receptors, Scavenger / genetics
  • Receptors, Scavenger / metabolism

Substances

  • CD36 Antigens
  • Lipoproteins, LDL
  • Receptors, Scavenger
  • oxidized low density lipoprotein
  • Glucose