ConCOEUR

Abstract

Aortic valve stenosis (AVS) is the most prevalent valvular heart disorder and the third most common cause of cardiovascular disease in the western world. AVS is characterized by progressive narrowing, fibrosis and calcification of the aortic valve (AV), which ultimately interfere with proper blood ejection from the heart. Traditionally viewed as a mere valve disorder, AVS is now recognized as a central cause of left ventricle hypertrophy. Aortic valve replacement is the standard of care for severe symptomatic AVS patients, improving quality of life and long-term survival. However, most patients have a long asymptomatic period, which hampers timely diagnosis and intervention. Therefore, it is vital to identify novel therapies to hinder AVS and left ventricle dysfunction, as well as risk stratification markers aiming to improve patient prognosis.

Hence, the long-term goal of the proposal was to unveil the function of nuclear Cx43 and its impact on cardiovascular diseases. Particularly, we hypothesized that injury-induced accumulation of nuclear Cx43 regulates the expression of genes that drive AVS progression and cardiac hypertrophy. ConCOEUR constitutes a decisive contribution not only to elucidate the auspicious non-canonical role of Cx43 upon gene transcription, but also its pathophysiological relevance in AVS progression.