Abstract 16981: Proteomic Profiles of Diabetic Heart Failure Report on Myocardial Metabolism, Ventricular Hypertrophy, and Endothelial Dysfunction

Abstract

Introduction: There is a complex epidemiologic relationship between type two diabetes mellitus (DM) and heart failure (HF), and it is unclear whether the biochemical basis of HF differs in patients with and without DM. Hypothesis: Proteomic profiling of myocardial tissue from patients with and without DM will identify unique signatures of diabetic HF. Methods: Using the Olink aptamer-based platform, we performed proteomic profiling of 552 proteins on 37 myocardial tissue samples: 9 controls, 10 with HF, 7 with DM, and 11 with HF+DM. One-way ANOVA was first used to identify proteins that differed across the four groups. Associated proteins were then tested for differences between HF+DM and each other group independently; we retained proteins with the same direction of effect for each comparison. Each analysis was controlled for false discovery rate (q<0.1). Results: We identified 12 proteins that differed significantly between HF+DM and all three other groups. Among these, six proteins were significant after FDR adjusted ANOVA and had the same direction of effect. These included 5’-NT (q=5.35E-07), a regulator of intracellular energy utilization, and carboxypeptidase A2, a metalloprotease that cleaves peptides during digestion (q=0.0003). Expression of myocardial leptin receptors (q=0.001), complement factor H related protein (q=0.003), and carbonic anhydrase (q=0.006) were also upregulated in diabetic HF, and have previously been linked to myocyte hypertrophy. Markers of endothelial dysfunction - ESM-1 (q=5.62E-06) and VEGFR-3 (q=0.024) - were also increased in HF+DM myocardium as compared to other groups (Figure 1). Conclusions: Proteomic profiling of HF, DM, and HF+DM myocardial tissue suggest alterations in intracellular energy substrate utilization as well as increased expression of tissue biomarkers previously associated with ventricular hypertrophy and myocardial remodeling.