LDL associates with pro-inflammatory monocyte subset differentiation and increases in chemokine receptor profile expression in African Americans. (1st July 2022)

• Record Type: Journal Article
• Authors: Gutierrez-Huerta, Cristhian A.; Turner, Briana S.; Claudel, Sophie E.; Farmer, Nicole; Islam, Rafique; Mitchell, Valerie M.; Collins, Billy S.; Baumer, Yvonne; Remaley, Alan T.; Powell-Wiley, Tiffany M.
• Is Part Of: International journal of cardiology. Volume 358(2022)
• Page Start: 88
• Page End: 93
• Publication Date: 2022-07-01
• Subjects: Health disparities -- Monocyte subset phenotype -- Cardiovascular disease -- LDL; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2022.04.038
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Background: In the United States, African Americans (AAs) have greater risk for Class III obesity and cardiovascular disease (CVD). Previous reports suggest that AAs have a different immune cell profile when compared to Caucasians. Methods: The immune cell profile of AAs was characterized by flow cytometry using two experimental setups: ex vivo (N = 40) and in vitro (N = 10). For ex vivo experiments, PBMC were treated with participant serum to understand how lipid contents may contribute to monocyte phenotypic differences. For in vitro experiments, monocytes were low-density lipoprotein (LDL)- or vehicle-treated for four hours and subsequently analyzed by flow cytometry and RT-qPCR. Results: When PBMCs were treated with participant sera, subsequent multivariable regression analysis revealed that serum triglycerides and LDL levels were associated with monocyte subset differences. In vitro LDL treatment of monocytes induced a phenotypic switch in monocytes away from classical monocytes accompanied by subset-specific chemokine receptor CCR2 and CCR5 expression changes. These observed changes are partially translation-dependent as determined by co-incubation with cycloheximide. Conclusions: LDL treatment of monocytes induces a change in monocyte subsets and increases CCR2/CCR5 expression in a subset-specific manner. Understanding the molecular mechanisms could prove to have CVD-related therapeutic benefits, especially in high-risk populations with hyperlipidemia and increased risk for CVD. Graphical abstract: LDL associated changes on monocyte subsets and CCR2/5 expression. Unlabelled Image Highlights: Little is known about the impact of LDL cholesterol on monocytes in African Americans. LDL cholesterol is associated with monocyte phenotypes in African Americans. LDL promotes monocyte subsets and monocyte chemokine receptor expression in a subset-specific way in vitro . LDL-induced changes are partly mediated by translation in a subset-specific manner.