Aims of our lab are also to identify novel mechanisms and to characterize specific signaling pathways involved in disease with the ultimate goal of understanding the molecular basis of valve disease. Calcific aortic valve disease (CAVD) is the third most common cause of cardiovascular disease in the Western world and the prevalence of severe aortic regurgitation ranges between 0.5 and 2.7% in the general population. Most of these congenital defects do not produce disease until midlife, when they generate significant morbidity. In many cases, the underlying causes of aortic valve disease have not been identified. It is essential to identify new disease markers and to gain knowledge about the molecular and cellular disease mechanisms, to be able to design preventive of therapeutical treatments. We are using different animal models to study the mechanisms leading to bicuspid aortic valve and CAVD. In diseased heart valves, there is distinct loss of extra-cellular matrix (ECM) organization associated with changes in mechanical proprieties that ultimately leads to dysfunction (Schoen, 2005). However, the molecular events that result in aberrant ECM expression and distribution characteristic of valve disease are largely unknown. We have recently discovered that the zinc finger containing transcription factor Krox20/Egr-2, a critical regulator of hindbrain development, is required for aortic valve development and for ECM organization.
