APOC2 protein as a cornerstone in the development of Aortic stenosis, in patients with Type 2 diabetes mellitus

Aortic stenosis (AS) and diabetes mellitus (DM) are both progressive diseases that if left untreated, result in significant morbidity and mortality. Several studies revealed that the prevalence of DM is substantially higher in patients with AS and, thus, the progression from mild to severe AS is greater in those patients with DM. Our goal is presenting a method for the treatment, prognosis and/or diagnosis of both diseases. A multi-omic strategy was performed in a cohort of 47 patients with AS and with or without DM. In the discovery phase, we analyzed aortic valve tissue, calcified and non-calcified, by Tandem Mass Tag (TMT) and, by Transcriptome sequencing using RNA-Seq. Then, For the quantitative analysis, the ratio of calcified:non-calcified tissue of each patient was compared. After the statistical analysis of the proteome and transcriptome of the AVs from patients with DAS, with or without DM, the results were compared to evaluate the correlation between them and to identify robust biomarkers for possible clinical use.

The APOC2 protein and APOC2 gene gave a p-value < 0.05 and a fold change (FC) > 1.5 in both analyses, and these values moved in the same direction between the study groups Thus, the APOC2 protein was considered the most robust potential biomarker since it was identified in both the proteomic and transcriptomic analysis, and moreover, it was confirmed in plasma samples from an independent cohort of patients when studied by ELISA and turbidimetry. Using both these techniques, the amounts of this protein were higher in the group of diabetic patients relative to the non-diabetic patients (ELISA p-value = 0.018; turbidimetry p-value = 0.038).

Therefore, the present study aims to resolve an unmet medical need to achieve a diagnosis of AS in patients with T2DM.