Abstract

Extracellular nucleotide metabolism controls thrombosis and inflammation and may affect degeneration and calcification of aortic valve prostheses. We evaluated the effect of different decellularization strategies on enzyme activities involved in extracellular nucleotide metabolism. Porcine valves were tested intact or decellularized either by detergent treatment or hypotonic lysis and nuclease digestion. The rates of ATP hydrolysis, AMP hydrolysis, and adenosine deamination were estimated by incubation of aorta or valve leaflet sections with substrates followed by HPLC analysis. We demonstrated relatively high activities of ecto-enzymes on porcine valve as compared to the aortic wall. Hypotonic lysis/nuclease digestion preserved >80 % of ATP and AMP hydrolytic activity but reduced adenosine deamination to <10 %. Detergent decellularization completely removed (<5 %) all these activities. These results demonstrate high intensity of extracellular nucleotide metabolism on valve surface and indicate that various valve decellularization techniques differently affect ecto-enzyme activities that could be important in the development of improved valve prostheses.

Highlights

  • Calcific aortic valve disease (CAVD) is a progressive disorder that increasingly afflicts the aging population

  • In order to examine the extracellular adenine nucleotide catabolism, the rates of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) hydrolysis as well as adenosine degradation were tested on the native valve surface

  • The step was to investigate, whether the aortic valve decellularization process affects the activities of extracellular nucleotide metabolism, what is important in terms of valvular prostheses adaptation

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Summary

Introduction

Calcific aortic valve disease (CAVD) is a progressive disorder that increasingly afflicts the aging population. This disease appears as a result of thickening and calcification of the aortic valve leaflets and could have form of aortic sclerosis (in the absence of obstruction in blood flow at the valve level) or aortic stenosis (with obstruction to ventricular outflow) [1]. Left ventricular hypertrophy caused by severe aortic stenosis is associated with sudden death, congestive heart failure, and stroke [2]. (2016) 9:119–126 patients over age 65, whereas aortic stenosis occurs in 2 to 5 % of the eldest patients, and it is the second most common indication for cardiac surgery [3, 4]. Aortic valve replacement (AVR) and transcatheter aortic valve implantation (TAVI) have become routine procedures with the number rising considerably over the last years [5, 6]

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