Extracellular nucleotide catabolism in aortoiliac bifurcation of atherosclerotic ApoE/LDLr double knock out mice

Nucleosides Nucleotides Nucleic Acids. 2014;33(4-6):323-8. doi: 10.1080/15257770.2014.880478.

Abstract

Atherosclerosis is a consequence of diverse pathologies that could be affected by signaling mediated by nucleotides and their metabolites. Concentration of specific nucleotide derivatives in the proximity of purinergic receptors is controlled by extracellular enzymes such as ecto-nucleoside triphopsphate diphosphohydrolase (eNTPD), ecto-5'-nucleotidase (e5NT), and ecto-adenosine deaminase (eADA). To estimate changes in metabolism of extracellular nucleotides in the atherosclerotic vessel wall, aortoiliac bifurcation of ApoE/LDLr (-/-) mice was perfused with solution containing adenosine-5'-triphosphate (ATP), adenosine-5'-monophosphate (AMP) or adenosine. Formation of the product of eNTPD, e5NT or eADA was measured by high performance liquid chromatography (HPLC). The most significant difference between ApoE/LDLr (-/-) and wild-type mice was several times higher rate of conversion of adenosine to inosine catalyzed by eADA activity. This highlights potential decrease in intravascular adenosine concentration in atherosclerosis.

Keywords: Nucleotides; adenosine; adenosine deaminase; atherosclerosis; ecto-5′-nucleotidase; ecto-nucleoside triphopsphate diphosphohydrolase; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism
  • Adenosine Monophosphate / metabolism
  • Adenosine Triphosphate / metabolism
  • Animals
  • Aorta / pathology*
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Extracellular Space / enzymology
  • Extracellular Space / metabolism*
  • Iliac Artery / pathology*
  • Mice
  • Mice, Knockout
  • Nucleotides / metabolism*
  • Receptors, LDL / deficiency*
  • Receptors, LDL / genetics

Substances

  • Apolipoproteins E
  • Nucleotides
  • Receptors, LDL
  • Adenosine Monophosphate
  • Adenosine Triphosphate
  • Adenosine