Exploratory LC-MS/MS-Based Proteomic and Lipidomic Profiling of Plasma Samples from Premature Coronary Artery Disease Patients: A Pilot Study in a South Asian Population.

Premature coronary artery disease (PCAD) is a growing public health concern, especially in South Asia, where traditional risk factors fail to fully explain the increasing incidence of early-onset myocardial infarction. To explore its molecular underpinnings, we conducted a pilot study analyzing plasma proteins and lipids to identify potential biomarkers and dysregulated pathways associated with PCAD. Label-free quantitative proteomics revealed distinct molecular signatures separating PCAD patients from age- and sex-matched healthy controls. Key alterations included upregulation of GALE, immunoglobulin genes, and KIF20B, suggesting enhanced inflammatory responses and proliferative activity associated with post-myocardial infarction cellular repair. Similarly, down regulations of various proteins linked to multiple functions, such as myocardial infarction, hemoglobinopathy, complement and coagulation cascade, and fatty acid and lipoprotein transport in hepatocytes, were observed. Untargeted lipidomics further revealed significant elevations in several phosphatidylcholine species (PC 42:5, PC 40:3, and PC 42:7), highlighting disruption of highly unsaturated phospholipid metabolism. Overall, these findings indicate that PCAD is a multifactorial disorder involving metabolic, immune, and vascular dysfunction beyond conventional lipid abnormalities, underscoring the need for larger cohort studies to validate these biomarkers and uncover novel therapeutic targets.