Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Role of the Scavenger Receptor CD36 in Accelerated Diabetic Atherosclerosis

Version 1 : Received: 2 August 2020 / Approved: 4 August 2020 / Online: 4 August 2020 (10:37:01 CEST)

A peer-reviewed article of this Preprint also exists.

Navas-Madroñal, M.; Castelblanco, E.; Camacho, M.; Consegal, M.; Ramirez-Morros, A.; Sarrias, M.R.; Perez, P.; Alonso, N.; Galán, M.; Mauricio, D. Role of the Scavenger Receptor CD36 in Accelerated Diabetic Atherosclerosis. Int. J. Mol. Sci. 2020, 21, 7360. Navas-Madroñal, M.; Castelblanco, E.; Camacho, M.; Consegal, M.; Ramirez-Morros, A.; Sarrias, M.R.; Perez, P.; Alonso, N.; Galán, M.; Mauricio, D. Role of the Scavenger Receptor CD36 in Accelerated Diabetic Atherosclerosis. Int. J. Mol. Sci. 2020, 21, 7360.

Abstract

Diabetes mellitus entails increased atherosclerotic burden and medial arterial calcification but the precise mechanisms are not fully elucidated. Our aim was 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 medium containing normal (5 mM) or high glucose (22 mM) for 72 h with or without oxLDL (24 h). The uptake of DiI-labelled oxLDL was quantified by flow citometry and fluorimetry and calcification assays were performed in VSMC cultured in osteogenic medium and stained by alizarin red. We observed an 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-labelled oxLDL was increased after exposure to high glucose. Silencing of CD36 abolished the induction of CD36 and reduced the expression of calcification enzymes and mineralization of VSMC. Our results indicate that CD36 signaling is involved in hyperglycemia and oxLDL-induced vascular calcification in diabetes.

Keywords

scavenger receptor CD36; inflammation; vascular calcification; diabetes; atherosclerosis

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

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