Enzymes of the purinergic signaling system exhibit diverse effects on the degeneration of valvular interstitial cells in a 3‐D microenvironment

What is it about?

Acquired aortic valve stenosis, also referred to as calcific aortic valve disease (CAVD), is the most common valvular disease in the US and Europe and is the second most frequent cause for cardiac surgery. It is largely a disease of the elderly people and patients typically present in the seventh or eighth decade of life. Despite the high prevalence and severe consequences of CAVD, its pathogenesis remains relatively poorly understood and lags far behind our knowledge of atherosclerosis, a disease to which CAVD is frequently compared. The process was thought to be 'degenerative' because of the time-dependent calcium deposition in the aortic valve leaflets, However, studies in the recent past suggest that CAVD is an active disease process with lipoprotein deposition, chronic inflammation and progressive leaflet degeneration. This study extends our understanding on the role of the purinergic signaling system in the degenerative remodeling of the aortic valve by using conventional cell culture experiments as well as novel three-dimensional culture models involving valvular interstitial cells, the most prevalent cells in the heart valve. Our findings suggest that dysregulation of enzymes of the purinergic signaling pathways play an important role in the initiation and propagation of degenerative events in aortic valves. With advancing therapy modalities in the clinical field and growing interest in underlying biological events triggering aortic valve degeneration this paper provides additional insight that increases our understanding in this field and may serve for modification of biological heart valve prostheses to prevent degeneration and extent their durability.

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