Abstract 341: Nucleotide Triphosphate Diphosphohydrolase-1 (NTPDase1) Overexpression Improves Post-Myocardial Infarction Recovery

Background: With myocardial injury extracellular levels of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) increase. These extracellular ATP and ADP levels are modulated via hydrolysis by triphosphate diphosphohydrolase-1 (NTDP-1/CD39) to adenosine monophosphate (AMP) subsequently converted by ecto-5’-nucleotidase (CD73) to adenosine. Previous data demonstrated significantly smaller infarcts in mice globally overexpressing NTPDase1. The current objective was to determine whether global overexpression of NTPDase1 would beneficially or detrimentally affect post-infarction myocardial recovery. Methods: Myocardial infarction was induced by permanent coronary artery ligation in transgenic mice overexpressing human NTPDase1 driven by the murine H-2Kb (MHC class I) promoter in mice. Survival, myocardial function and BNP were measured to assess the effect on post-infarction myocardial recovery. Results: Following permanent coronary artery ligation there was decreased mortality in NTPDase1-Tg animals compared to WT animals (Fig A). Echocardiographic assessment of ejection fraction revealed that compared to baseline the post-MI EF of NTPDase1-Tg mice was not significantly diminished (Fig. B). Consistent with preserved cardiac function, plasma levels of brain natriuretic peptide (BNP) were significantly reduced in NTPDase1-Tg mice versus WT littermate control mice at post-MI day 28 (Fig. C). Conclusions: Overexpression of NTPDase1 improves post-infarction myocardial recovery.