Loss of ectonucleotidases from the coronary vascular bed after ischemia-reperfusion in isolated rat heartReport as inadecuate




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BMC Cardiovascular Disorders

, 13:53

Coronary artery disease

Abstract

BackgroundEctonucleotidase plays an important role in the regulation of cardiac function by controlling extracellular levels of adenine nucleotides and adenosine. To determine the influence of ischemia-reperfusion injury on ectonucleotidase activity in coronary vascular bed, we compared the metabolic profile of adenine nucleotides during the coronary circulation in pre- and post-ischemic heart.

MethodsLangendorff-perfused rat hearts were used to assess the intracoronary metabolism of adenine nucleotides. The effects of ischemia on the adenine nucleotide metabolism were examined after 30 min of ischemia and 30 min of reperfusion. Adenine nucleotide metabolites were measured by high performance liquid chromatography.

ResultsATP, ADP and AMP were rapidly metabolized to adenosine and inosine during the coronary circulation. After ischemia, ectonucleotidase activity of the coronary vascular bed was significantly decreased. In addition, the perfusate from the ischemic heart contained a considerable amount of enzymes degrading ATP, AMP and adenosine. Immunoblot analysis revealed that the perfusate from the ischemic heart dominantly contained ectonucleoside triphosphate diphosphohydrolase 1, and, to a lesser extent, ecto-5’-nucleotidase. The leakage of nucleotide metabolizing enzymes from the coronary vascular bed by ischemia-reperfusion was more remarkable in aged rats, in which post-ischemic cardiac dysfunction was more serious.

ConclusionEctonucleotidases were liberated from the coronary vascular bed by ischemia-reperfusion, resulting in an overall decrease in ectonucleotidase activity in the post-ischemic coronary vascular bed. These results suggest that decreased ectonucleotidase activity by ischemia may exacerbate subsequent reperfusion injury, and that levels of circulating ectonucleotidase may reflect the severity of ischemic vascular injury.

KeywordsIschemia-reperfusion Coronary circulation Ectonucleotidase ATP Adenosine AbbreviationsAdoAdenosine

ADAAdenosine deaminase

CD73Ecto-5’-nucleotidase

CD39Ectonucleoside triphosphate diphosphohydrolases 1

EDTAEthylenediaminetetraacetic acid

eATP1,N-etheno adenosine-5’-triphosphate

eADP1,N-etheno adenosine-5’-diphosphate

eAMP1,N-etheno adenosine-5’-monophosphate

eAdo1,N-etheno adenosine

ENTPDEctonucleoside triphosphate diphosphohydrolases

HPLCHigh performance liquid chromatography

αβ-MeADP: α,β-methylene adenosine diphosphate.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2261-13-53 contains supplementary material, which is available to authorized users.

Kaoru Takahashi-Sato and Isao Matsuoka contributed equally to this work.

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Author: Kaoru Takahashi-Sato - Masahiro Murakawa - Junko Kimura - Masa-aki Ito - Isao Matsuoka

Source: https://link.springer.com/article/10.1186/1471-2261-13-53







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