Circulating CD36 is increased in hyperlipidemic mice: Cellular sources and triggers of release

Free Radic Biol Med. 2021 May 20;168:180-188. doi: 10.1016/j.freeradbiomed.2021.03.004. Epub 2021 Mar 26.

Abstract

CD36 is a multifunctional transmembrane glycoprotein abundantly expressed in several cell types. Recent studies have identified CD36 in circulation (cCD36) in several chronic inflammatory diseases, including type 2 diabetes and chronic kidney disease, and proposed cCD36 to be a biomarker of disease activity. Whether cCD36 is present in hyperlipidemia, a condition characterized by oxidative stress and low-grade inflammation, is not known. In addition, the cellular origin of cCD36 and triggers of CD36 release have not been elucidated. We now demonstrate that plasma cCD36 level is increased in hyperlipidemic ApoE-/- and Ldlr-/- mice. Using several cell-specific CD36 knockout mice, we showed that multiple cell types contribute to cCD36 generation in hyperlipidemic conditions, with a particularly strong contribution from endothelial cells. In vitro studies have demonstrated that oxidized phospholipids, ligands for CD36 (oxPCCD36), which are known to accumulate in circulation in hyperlipidemia, induce a robust release of CD36 from several cell types. In vivo studies have demonstrated CD36 release into the circulation of WT mice in response to tail-vein injection of oxPCCD36. These findings document the presence of cCD36 in hyperlipidemia and identify a link between cCD36 and oxidized phospholipids generated under oxidative stress and low-grade inflammation associated with hyperlipidemia.

Keywords: Adipocytes; Circulating CD36; Dyslipidemia; Endothelial cells; Lipid oxidation; Macrophages; Oxidized phospholipids (oxPC); Platelets; Scavenger receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD36 Antigens / genetics
  • CD36 Antigens / metabolism
  • Diabetes Mellitus, Type 2*
  • Endothelial Cells* / metabolism
  • Lipoproteins, LDL / metabolism
  • Mice
  • Mice, Knockout
  • Oxidation-Reduction

Substances

  • CD36 Antigens
  • Cd36 protein, mouse
  • Lipoproteins, LDL