Low Density Lipoprotein Cholesterol Decreases the Expression of Adenosine A 2A Receptor and Lipid Rafts-Protein Flotillin-1: Insights on Cardiovascular Risk of Hypercholesterolemia

• Published in: Cells (Basel, Switzerland) Vol. 13; no. 6
• Main Authors: Chaptal, Marie-Charlotte, Maraninchi, Marie, Musto, Giorgia, Mancini, Julien, Chtioui, Hedi, Dupont-Roussel, Janine, Marlinge, Marion, Fromonot, Julien, Lalevee, Nathalie, Mourre, Florian, Beliard, Sophie, Guieu, Régis, Valero, René, Mottola, Giovanna
• Format: Journal Article
• Language: English
• Published: Switzerland 11-03-2024
• Subjects: Adenosine; Cardiovascular Diseases; Carrier Proteins; Cholesterol; Cholesterol, LDL - metabolism; Heart Disease Risk Factors; Humans; Hypercholesterolemia; Leukocytes, Mononuclear - metabolism; Membrane Microdomains - metabolism; Membrane Proteins; Receptor, Adenosine A2A - metabolism; Risk Factors; Flotillin-1; lipid rafts; LDL-C; adenosine receptor; cholesterol; cardiovascular risk; hypercholesterolemia
• ISSN: 2073-4409

High blood levels of low-density lipoprotein (LDL)-cholesterol (LDL-C) are associated with atherosclerosis, mainly by promoting foam cell accumulation in vessels. As cholesterol is an essential component of cell plasma membranes and a regulator of several signaling pathways, LDL-C excess may have wider cardiovascular toxicity. We examined, in untreated hypercholesterolemia (HC) patients, selected regardless of the cause of LDL-C accumulation, and in healthy participants (HP), the expression of the adenosine A
receptor (A
R), an anti-inflammatory and vasodilatory protein with cholesterol-dependent modulation, and Flotillin-1, protein marker of cholesterol-enriched plasma membrane domains. Blood cardiovascular risk and inflammatory biomarkers were measured. A
R and Flotillin-1 expression in peripheral blood mononuclear cells (PBMC) was lower in patients compared to HP and negatively correlated to LDL-C blood levels. No other differences were observed between the two groups apart from transferrin and ferritin concentrations. A
R and Flotillin-1 proteins levels were positively correlated in the whole study population. Incubation of HP PBMCs with LDL-C caused a similar reduction in A
R and Flotillin-1 expression. We suggest that LDL-C affects A
R expression by impacting cholesterol-enriched membrane microdomains. Our results provide new insights into the molecular mechanisms underlying cholesterol toxicity, and may have important clinical implication for assessment and treatment of cardiovascular risk in HC.