Background
Calcific Aortic Valve Disease (CAVD) is the most common etiology of acquired valve disease. Initial phases of CAVD include thickening of the cusps, whereas advanced stages are associated with biomineralization and reduction of the aortic valve area. These conditions are known as Aortic Valve Sclerosis (AVSc) and Aortic Valve Stenosis (AVS), respectively. Due to its asymptomatic presentation, little is know about the molecular determinants of AVSc. The aim of this study is to correlate plasma and tissue Osteopontin (OPN) levels with echocardiographic evaluation for the identification of asymptomatic patients at risk of CAVD. In addition, we aim to analyze the differential expression and biological function of OPN splicing variants as biomarkers of early and late stages of CAVD.
Methods
From Jan 2010 to Feb 2011, 254 patients were enrolled in the study. Subjects were divided in three groups based on transesophageal echocardiographic (TEE) evaluation: Controls (56 subjects), AVSc (90), and AVS (164). Plasma and tissue OPN levels were measured by IHC, ELISA and qPCR.
Results
Patients with AVSc have and AVS higher OPN levels compared to controls. OPN levels are elevated in asymptomatic AVSc patients with no appearance of calcification during TEE evaluation. Osteopontin splicing variants -a, -b, and -c are differentially expressed during CAVD progression and are able to inhibit biomineralization in a cell-based biomineralization assay.
Conclusions
The analysis of the differential expression of OPN splicing variants during CAVD may help in developing diagnostic and risk stratification tools to follow the progression of asymptomatic AV degeneration.