Genetic polymorphisms in cardiovascular disease (CVD) susceptibility across different ethnic groups is highly imperetive. Therefore, it is of interest to investigate the role of genetic polymorphisms Show more
Genetic polymorphisms in cardiovascular disease (CVD) susceptibility across different ethnic groups is highly imperetive. Therefore, it is of interest to investigate the role of genetic polymorphisms in cardiovascular disease (CVD) susceptibility across different ethnic groups. Participants were tested for variations in LDLR, APOE and LPL genes and their association with cardiovascular risk factors such as cholesterol levels and blood pressure was examined. Data shows ethnic differences in the prevalence of these polymorphisms, suggesting that genetic factors contribute to CVD risk in a population-specific manner. Thus, we show the need for personalized cardiovascular risk assessment strategies. The ethnic-specific distribution of genetic polymorphisms (LDLR, APOE and LPL) linked to cardiovascular disease susceptibility, highlighting the need for personalized cardiovascular risk assessment strategies based on genetic and ethnic factors is highlighted. Show less
Dendritic cells (DCs) undergo rapid metabolic reprogramming to generate signal-specific immune responses. The fine control of cellular metabolism underlying DC immune tolerance remains elusive. We hav Show more
Dendritic cells (DCs) undergo rapid metabolic reprogramming to generate signal-specific immune responses. The fine control of cellular metabolism underlying DC immune tolerance remains elusive. We have recently reported that NCoR1 ablation generates immune-tolerant DCs through enhanced IL-10, IL-27 and SOCS3 expression. In this study, we did comprehensive metabolic profiling of these tolerogenic DCs and identified that they meet their energy requirements through enhanced glycolysis and oxidative phosphorylation (OXPHOS), supported by fatty acid oxidation-driven oxygen consumption. In addition, the reduced pyruvate and glutamine oxidation with a broken TCA cycle maintains the tolerogenic state of the cells. Mechanistically, the AKT-mTOR-HIF-1α-axis mediated glycolysis and CPT1a-driven β-oxidation were enhanced in these tolerogenic DCs. To confirm these observations, we used synthetic metabolic inhibitors and found that the combined inhibition of HIF-1α and CPT1a using KC7F2 and etomoxir, respectively, compromised the overall transcriptional signature of immunological tolerance including the regulatory cytokines IL-10 and IL-27. Functionally, treatment of tolerogenic DCs with dual KC7F2 and etomoxir treatment perturbed the polarization of co-cultured naïve CD4 Show less