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

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 (oxPC_CD36), 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 oxPC_CD36. 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.

SUBMITTER: Biswas S

PROVIDER: S-EPMC8085123 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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

Biswas Sudipta S Gao Detao D Altemus Jessica B JB Rekhi Umar R UR Chang Ellen E Febbraio Maria M Byzova Tatiana V TV Podrez Eugene A EA

Free radical biology & medicine 20210326

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 ...[more]

PMID: 33775772

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Project description:ObjectiveElevated plasma levels of the fatty acid transporter, CD36, have been shown to constitute a novel biomarker for type 2 diabetes mellitus (T2DM). We recently reported such circulating CD36 to be entirely associated with cellular microparticles (MPs) and aim here to determine the absolute levels and cellular origin(s) of these CD36+MPs in persons with T2DM.DesignAn ex vivo case-control study was conducted using plasma samples from 33 obese individuals with T2DM (body mass index (BMI)=39.9±6.4 kg m(-2); age=57±9 years; 18 male:15 female) and age- and gender-matched lean and obese non-T2DM controls (BMI=23.6±1.8 kg m(-2) and 33.5±5.9 kg m(-2), respectively). Flow cytometry was used to analyse surface expression of CD36 together with tissue-specific markers: CD41, CD235a, CD14, CD105 and phosphatidyl serine on plasma MPs. An enzyme-linked immunosorbent assay was used to quantify absolute CD36 protein concentrations.ResultsCD36+MP levels were significantly higher in obese people with T2DM (P<0.00001) and were primarily derived from erythrocytes (CD235a+=35.8±14.6%); although this did not correlate with haemoglobin A(1c). By contrast, the main source of CD36+MPs in non-T2DM individuals was endothelial cells (CD105+=40.9±8.3% and 33.9±8.3% for lean and obese controls, respectively). Across the entire cohort, plasma CD36 protein concentration varied from undetectable to 22.9 μg ml(-1) and was positively correlated with CD36+MPs measured by flow cytometry (P=0.0006) but only weakly associated with the distribution of controls and T2DM (P=0.021). Multivariate analysis confirmed that plasma CD36+MP levels were a much better biomarker for diabetes than CD36 protein concentration (P=0.009 vs P=0.398, respectively).ConclusionsBoth the levels and cellular profile of CD36+MPs differ in T2DM compared with controls, suggesting that these specific vesicles could represent distinct biological vectors contributing to the pathology of the disease.

Dataset Information

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

Publications

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

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