Aortic Valve Stenosis

A. Akhmedov Group Leader, PhD

Calcific aortic valve stenosis represents the most common form of valvular heart disease in the developed world, affecting roughly 2.8% of the general population above 75 years of age. Symptomatic calcific aortic valve stenosis impairs the quality of life of affected individuals dramatically, incurring considerable morbidity and mortality. Indeed, in patients with symptomatic aortic stenosis the rate of death exceeds 50% at 2 years unless aortic valve-replacement is initiated, thus posing a major societal and economic burden. In marked contrast to the old-fashioned concept, that aortic stenosis is a degenerative disease, it is now broadly accepted that calcific aortic stenosis is a chronic condition that is driven by an active biological process at the molecular and cellular level. Of note, the clustering seen within families and the heterogeneity of its geographical distribution suggest that differences in the genetic background may play a crucial. Presently, however, with no pharmaceutical treatment graspable, surgical or transcatheter aortic valve (TAVI) replacement is the only treatment option currently available in our armamentarium. Importantly, these treatment options are used at very late stages of the disease process and are associated with a not negligible peri-operative risk. Unfortunately, so far no pharmaceutical therapy proved effective to halt disease progression, possibly because the molecular underpinnings of disease initiation and progression are insufficiently characterized. While lipoprotein homing, chronic inflammation and osteoblastic transition of valve interstitial cells is broadly accepted to represent cornerstones in the pathogenesis of calcific aortic stenosis, the molecular pathways by which these processes are fuelled by remain elusive. Our research group aims to investigate the novel molecular pathways involved in aortic valve stenosis progression that might help the development of pharmaceutical interventions to halt disease progression.