UTP reduces infarct size and improves mice heart function after myocardial infarct via P2Y 2 receptor

R. Cohen, A. Shainberg, Edith Hochhauser, Y. Cheporko, A. Tobar, E. Birk, L. Pinhas, J. Leipziger, J. Don, E. Porat

Research output: Contribution to journalArticlepeer-review

Abstract

Pyrimidine nucleotides are signaling molecules, which activate G protein-coupled membrane receptors of the P2Y family. P2Y 2 and P2Y 4 receptors are part of the P2Y family, which is composed of 8 subtypes that have been cloned and functionally defined. We have previously found that uridine-5′-triphosphate (UTP) reduces infarct size and improves cardiac function following myocardial infarct (MI). The aim of the present study was to determine the role of P2Y 2 receptor in cardiac protection following MI using knockout (KO) mice, in vivo and wild type (WT) for controls. In both experimental groups used (WT and P2Y 2 -/- receptor KO mice) there were 3 subgroups: sham, MI, and MI + UTP. 24 h post MI we performed echocardiography and measured infarct size using triphenyl tetrazolium chloride (TTC) staining on all mice. Fractional shortening (FS) was higher in WT UTP-treated mice than the MI group (44.7 ± 4.08% vs. 33.5 ± 2.7% respectively, p < 0.001). However, the FS of P2Y 2 -/- receptor KO mice were not affected by UTP treatment (34.7 ± 5.3% vs. 35.9 ± 2.9%). Similar results were obtained with TTC and hematoxylin and eosin stainings. Moreover, troponin T measurements demonstrated reduced myocardial damage in WT mice pretreated with UTP vs. untreated mice (8.8 ± 4.6 vs. 12 ± 3.1 p < 0.05). In contrast, P2Y 2 -/- receptor KO mice pretreated with UTP did not demonstrate reduced myocardial damage. These results indicate that the P2Y 2 receptor mediates UTP cardioprotection, in vivo.

Original languageEnglish
Pages (from-to)1126-1133
Number of pages8
JournalBiochemical Pharmacology
Volume82
Issue number9
DOIs
StatePublished - 1 Nov 2011
Externally publishedYes

Keywords

  • Cardioprotection
  • Ischemia
  • Knockout mice
  • P2Y receptor
  • UTP

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