Transcriptional regulation of heart valve development and disease

Aortic valve disease is estimated to affect 2% of the United States population. There is increasing evidence that aortic valve disease has a basis in development, as congenital valve malformations are prevalent in patients undergoing valve replacement surgery. In fact, a number of genetic mutations have been linked to valve malformations and disease. In the initial stages of aortic valve pathogenesis, the valvular interstitial cells become activated, undergo cell proliferation, and participate in extracellular matrix remodeling. Many of these cell properties are shared with mesenchymal progenitor cells of the normally developing valves and bones. Historically, valve calcification was thought to be a passive process reflecting end-stage disease. However, recent evidence describes the increased expression of transcription factors in diseased AoV that are common to valvulogenic and osteogenic processes. These studies lend support to the idea that a developmental gene program is reactivated in aortic valve disease and may contribute to the molecular mechanisms underlying valve calcification in disease.