Proteomics Profiling of Early Coronary Artery Injury in a Rat Model of Type 1 Diabetes Mellitus

Abstract

Individuals with type 1 diabetes mellitus (T1DM) experience an increased risk of cardiovascular disease (CVD). To improve early detection and prevention strategies, a better understanding of early vascular changes is needed. Although coronary artery (CA) damage is a known T1DM complication, its underlying proteomic basis remains unclear. This study used a proteomic approach to identify differentially expressed proteins in the CAs of T1DM rat models, with the goal of identifying novel proteins and pathways associated with early diagnosis and prevention of CA complications. We established a streptozotocin-induced T1DM model in male Sprague–Dawley rats and conducted tandem mass tag-based quantitative proteomics and bioinformatics analyses to investigate protein expression profiles in CAs. The analyses identified 443 differentially expressed proteins, with 229 upregulated and 214 downregulated proteins. Functional annotation and pathway enrichment analyses revealed that these proteins primarily participate in lipid metabolism, the peroxisome proliferator-activated receptor (PPAR) signaling pathway, peroxisome function, and butanoate metabolism. Validation experiments using Western blotting analysis and quantitative real-time PCR confirmed significant upregulation of 3-hydroxy-3-methylglutaryl coenzyme A synthase 2 (HMGCS2), fatty acid-binding protein 4 (FABP4), and platelet glycoprotein 4 (CD36) at the protein and mRNA levels in diabetic rat CAs, consistent with the proteomic results. Our findings indicate that HMGCS2, FABP4, and CD36 may serve as important molecular markers for the early diagnosis or therapeutic targeting of CA damage in T1DM. The observed molecular changes appear to be linked to the PPAR signaling pathway.

Clinical trial registration. Not applicable.