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Adenosine 2A receptor modulates inflammation and phenotype in experimental abdominal aortic aneurysms
Author(s) -
Bhamidipati Castigliano M.,
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
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-214197
Subject(s) - adenosine a2a receptor , agonist , inflammation , chemistry , medicine , elastase , receptor , endocrinology , adenosine receptor , immunology , pharmacology , biochemistry , enzyme
Activation of the adenosine 2A receptor (A 2A R) 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 A 2A R‐knockout (A 2A RKO) and C57BL6/J wild‐type (WT) mice resulted in nearly 100% larger aneurysms in A 2A RKO compared to WT 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 2A R antagonism in elastase‐perfused WT mice also resulted in larger aneurysms ( P <0.05), while A 2A R agonism limited aortic dilatation ( P <0.05). Activated Thy‐1.2 + T lymphocytes from WT mice treated in vitro with A 2A R antagonist increased cytokine production, and treatment with A 2A R agonist decreased cytokine production ( P <0.05 for all). Primary activated CD4 + T lymphocytes from A 2A RKO mice exhibited greater chemotaxis ( P <0.05). A 2A R antagonist increased chemotaxis of activated CD4 + cells from WT mice in vitro , and A 2A R agonist reduced this effect ( P <0.05). A 2A R activation attenuates AAA formation partly by inhibiting immune cell recruitment and reducing elastin fragmentation. These findings support augmenting A 2A R signaling as a putative target for limiting aneurysm formation.—Bhamidipati, C. M., Mehta, G. S., Moehle, C. W., Meher, A. K., Su, G., Vigneshwar, N. G., Barbery, C., Sharma, A. K., Kron, I. L., Laubach, V. E., Owens, G. K., Upchurch Jr., G. R., Ailawadi, G. Adenosine 2A receptor modulates inflammation and phenotype in experimental abdominal aortic aneurysms. FASEB J. 27, 2122–2131 (2013). www.fasebj.org