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

Castigliano 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 journalArticle

6 Citations (Scopus)

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 1 2013
Externally publishedYes

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Purinergic P1 Receptors
Abdominal Aortic Aneurysm
Adenosine
Purinergic P1 Receptor Agonists
Purinergic P1 Receptor Antagonists
Inflammation
Aneurysm
Phenotype
Elastin
Pancreatic Elastase
Chemotaxis
Cytokines
T-Lymphocytes
T-cells
Knockout Mice
Dilatation
Perfusion
Chemical activation
Wounds and Injuries
Infiltration

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Bhamidipati, C., Mehta, G. S., Moehle, C. W., Meher, A. K., Su, G., Vigneshwar, N. G., ... Ailawadi, G. (2013). Adenosine 2A receptor modulates inflammation and phenotype in experimental abdominal aortic aneurysms. FASEB Journal, 27(6), 2122-2131. https://doi.org/10.1096/fj.12-214197

Adenosine 2A receptor modulates inflammation and phenotype in experimental abdominal aortic aneurysms. / Bhamidipati, Castigliano; Mehta, Gaurav S.; Moehle, Christopher W.; Meher, Akshaya K.; Su, Gang; Vigneshwar, Navin G.; Barbery, Carlos; Sharma, Ashish K.; Kron, Irving L.; Laubach, Victor E.; Owens, Gary K.; Upchurch, Gilbert R.; Ailawadi, Gorav.

In: FASEB Journal, Vol. 27, No. 6, 01.06.2013, p. 2122-2131.

Research output: Contribution to journalArticle

Bhamidipati, C, Mehta, GS, Moehle, CW, Meher, AK, Su, G, Vigneshwar, NG, Barbery, C, Sharma, AK, Kron, IL, Laubach, VE, Owens, GK, Upchurch, GR & Ailawadi, G 2013, 'Adenosine 2A receptor modulates inflammation and phenotype in experimental abdominal aortic aneurysms', FASEB Journal, vol. 27, no. 6, pp. 2122-2131. https://doi.org/10.1096/fj.12-214197
Bhamidipati, Castigliano ; Mehta, Gaurav S. ; Moehle, Christopher W. ; Meher, Akshaya K. ; Su, Gang ; Vigneshwar, Navin G. ; Barbery, Carlos ; Sharma, Ashish K. ; Kron, Irving L. ; Laubach, Victor E. ; Owens, Gary K. ; Upchurch, Gilbert R. ; Ailawadi, Gorav. / Adenosine 2A receptor modulates inflammation and phenotype in experimental abdominal aortic aneurysms. In: FASEB Journal. 2013 ; Vol. 27, No. 6. pp. 2122-2131.
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AU - Vigneshwar, Navin G.

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AU - Sharma, Ashish K.

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