Purinergic Ecto-Enzymes in Human and Ovine Aortic Valves: Indicators of Bacterial Nanocellulose Scaffold Cellularization

Abstract

Purinergic signalling plays a vital role in controlling the integrity of the aortic valve (AV) through metabolic and receptor effects of nucleotides (detrimental) and adenosine (protective). This study focused on characterizing a side-specific purinergic cascade: adenosine-5’-triphosphate (ATP) and adenosine-5’-monophosphate (AMP) hydrolysis rate and adenosine deamination rate in human non-stenotic and stenotic AVs, ovine native AVs, as well as a novel bacterial nanocellulose (BNC) bio-prosthesis in an ovine model. Human stenotic AVs were collected during replacement surgeries, while non-stenotic AVs came from heart transplant patients. Ovine native AVs were sourced from domestic sheep while the BNC prosthesis were collected six months post-implantation into the ovine aortas, with hemodynamic monitoring throughout. The results demonstrated that ecto-enzymes engaged in ATP metabolism are present in the ovine aortic valve, comparable to human valves. High activities of a beneficial adenosine enhancing ecto-enzyme pattern characterized the aortic and ventricular surfaces of human non-stenotic and ovine native aortic valves. In the human stenotic valve, especially on the aortic side, a detrimental phenotype of nucleotide-preserving ecto-enzymes was observed. The activities of nucleotide conversions were several times lower on the surface of the explanted BNC prosthesis than in the native valve, indicating some degree of cellularisation. These findings suggest that nucleotide-converting ecto-enzymes could serve as markers for the biological activity of AV prostheses, highlighting the need for further studies to enhance the cellularization of BNC prostheses.