Adenosine 2A receptor modulates inflammation and phenotype in experimental abdominal aortic aneurysms

Castigliano M. Bhamidipati, Gaurav S. Mehta, Christopher W. Moehle, Akshaya K. Meher, Gang Su, Navin G. Vigneshwar, Carlos Barbery, Ashish K. Sharma, Irving L. Kron, Victor E. Laubach, Gary K. Owens, Gilbert R. Upchurch, Gorav Ailawadi

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Activation of the adenosine 2A receptor (A2AR) reduces inflammation in models of acute injury but contribution in development of chronic abdominal aortic aneurysms (AAAs) is unknown. Elastase perfusion to induce AAA formation in A2AR-knockout (A2ARKO) and C57BL6/J wild-type (WT) mice resulted in nearly 100% larger aneurysms in A 2ARKO compared toWT at d 14 (P<0.05), with evidence of greater elastin fragmentation, more immune cell infiltration, and increased matrix metallatoproteinase (MMP) 9 expression (P<0.05). Separately, exogenous A 2AR antagonism in elastase-perfused WT mice also resulted in larger aneurysms (P<0.05), while A2AR agonism limited aortic dilatation (P<0.05). Activated Thy-1.2+ T lymphocytes from WT mice treated in vitro with A2AR antagonist increased cytokine production, and treatment with A2AR agonist decreased cytokine production (P<0.05 for all). Primary activated CD4+ T lymphocytes from A2ARKO mice exhibited greater chemotaxis (P<0.05). A2AR antagonist increased chemotaxis of activated CD4+ cells from WT mice in vitro, and A2AR agonist reduced this effect (P<0.05). A2AR activation attenuates AAA formation partly by inhibiting immune cell recruitment and reducing elastin fragmentation. These findings support augmenting A 2AR signaling as a putative target for limiting aneurysm formation.

Original languageEnglish (US)
Pages (from-to)2122-2131
Number of pages10
JournalFASEB Journal
Volume27
Issue number6
DOIs
StatePublished - Jun 2013

Keywords

  • Cd4 T lymphocytes
  • Gpcr signaling
  • Immune modulation
  • Inflammation
  • Physiological regulation

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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