Adenosine 2A receptor modulates inflammation and phenotype in experimental abdominal aortic aneurysms.
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 A2ARKO 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 A2AR 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 A2AR signaling as a putative target for limiting aneurysm formation.
['Bhamidipati|Castigliano M|CM|', 'Mehta|Gaurav S|GS|', 'Moehle|Christopher W|CW|', 'Meher|Akshaya K|AK|', 'Su|Gang|G|', 'Vigneshwar|Navin G|NG|', 'Barbery|Carlos|C|', 'Sharma|Ashish K|AK|', 'Kron|Irving L|IL|', 'Laubach|Victor E|VE|', 'Owens|Gary K|GK|', 'Upchurch|Gilbert R|GR|', 'Ailawadi|Gorav|G|']
D000241:Adenosine D058908:Adenosine A2 Receptor Agonists D058917:Adenosine A2 Receptor Antagonists D000818:Animals D017544:Aortic Aneurysm, Abdominal D015496:CD4-Positive T-Lymphocytes D016207:Cytokines D006801:Humans D007249:Inflammation D008297:Male D020780:Matrix Metalloproteinase 9 D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D010196:Pancreatic Elastase D010627:Phenethylamines D010641:Phenotype D043683:Receptors, Adenosine A2 D014227:Triazines D014230:Triazoles
inflammation CD4+ T lymphocytes GPCR signaling immune modulation physiological regulation