Apolipoprotein CII: Cornerstone of Pathophysiological Interplay in Aortic Stenosis and type 2 Diabetes Mellitus

Different studies have demonstrated that the progression from mild to severe calcific aortic stenosis (CAS) is faster in patients with type 2 Diabetes Mellitus (T2DM). Hence, we set out to find markers to improve the clinical management of individuals with both pathologies. Calcified and non-calcified valve tissue from patients with CAS, or with CAS and T2DM, was studied using a multiomics (proteomics and transcriptomics) strategy, highlighting the apolipoprotein CII (apoC2) protein as a potential biomarker. To define its diagnostic potential, we used ELISA and turbidimetry to measure the apoC2 in plasma from an independent cohort of patients. Moreover, an in vitro model of aortic valve interstitial cells (VICs) was used to evaluate the therapeutic potential of apoC2. This multiomics study demonstrated the increase in apoC2 protein and APOC2 gene expression in the valves of patients without T2DM. These changes were also reflected in their plasma, highlighting its potential as a diagnostic marker. Finally, exposure to recombinant apoC2 augments calcification and lipid deposition in VICs, effects that were dampened by silencing its expression, emphasizing the potential of apoC2 as therapeutic target. While the existence of T2DM affects the profile of the aortic valve, we have identified apoC2 as a potential diagnostic and therapeutic marker, an important step towards better clinical management that will help slow the progression of CAS in diabetic patients.