Vitamin D status affects proteomic profile of HDL-associated proteins and inflammatory mediators in dyslipidemia

Vitamin D deficiency and dyslipidemia have substantial implications for human health globally. Vitamin D is essential for bone metabolism and immune modulation, and its insufficiency is linked to various chronic inflammatory conditions. Dyslipidemia, characterized by low levels of high-density lipoprotein (HDL) and elevated levels of low-density lipoprotein (LDL) and triglycerides, is also prevalent. Previous research has shown a connection between vitamin D deficiency and low HDL, but the precise mechanism by which vitamin D influences HDL production and its anti-inflammatory properties remains unclear. This study aimed to investigate the proteomic profiles of individuals with and without vitamin D deficiency and dyslipidemia, specifically focusing on the effects of vitamin D on HDL production, its anti-inflammatory potential, and the molecular pathways associated with vitamin D deficiency and dyslipidemia, particularly inflammation and cancer pathways. By analyzing the proteomic profiles of 274 participants from the Qatar Biobank database, we identified 1301 proteins. Our findings indicated a decrease in HDL-associated apolipoproteins (ApoM and ApoD) in individuals with both dyslipidemia and vitamin D deficiency. Conversely, participants with these conditions exhibited increased expression of acute-phase proteins (SAA1 and SOD1), which are associated with inflammation. Pathway enrichment analysis revealed heightened inflammatory activity in individuals with vitamin D deficiency and dyslipidemia, with notable enrichments in pathways such as MAPK, JAK-STAT, Ras signaling, cytokine-cytokine receptor interaction, AGE-RAGE, ErbB signaling, and cancer pathways. Overall, cases of vitamin D deficiency showed enrichment in inflammation pathways, while individuals with both vitamin D deficiency and dyslipidemia demonstrated enhanced activation of cancer and inflammation pathways.