Functional effects of enhancing or silencing adenosine A2breceptors in cardiac fibroblasts

Yinghong Chen, Sara Epperson, Lala Makhsudova, Bruce Ito, Jorge Suarez, Wolfgang Dillmann, Francisco Villarreal
2004 American Journal of Physiology. Heart and Circulatory Physiology  
Cardiac fibroblasts (CF) express adenosine (ADO) receptors, and pharmacological evidence suggests the possible involvement of the A2 (A2a and A2b) receptor (A2aR and A2bR) subtypes in inhibiting cell functions involved in fibrosis. The main objective of this study was to define the contributions of A2a and/or A2b receptors in modulating ADO-induced decreases in CF functions. For this purpose, CF were either treated pharmacologically or had the A2aR or A2bR levels modified through the use of
more » ... mbinant adenovirus or siRNA. The assessment of mRNA expression in adult rat CF yielded evidence for A 1R, A2bR, A2aR, and A3R. Endogenously or exogenously enhanced ADO significantly inhibits CF proliferation, collagen, and protein synthesis. A 2R and A2aR agonists, although capable of inhibiting CF protein and collagen synthesis, were unable to define the contributions derived from A 2aR or A2bR. Overexpression of A 2bR in CF yielded significant decreases in basal levels of collagen and protein synthesis and correlated with increases in cAMP levels. However, at higher doses of ADO receptor agonists, significant increases in protein and collagen synthesis were observed. CF with underexpression of A 2bR yielded increases in protein and collagen synthesis. In contrast, A 2aR underexpression did not modify ADOinduced decreases in CF protein or collagen synthesis. In conclusion, results derived from the molecular manipulation of receptor levels indicate that A 2bR are critically involved in ADO-mediated inhibition of CF functions. collagen deposition; extracellular matrix; remodeling
doi:10.1152/ajpheart.00217.2004 pmid:15284071 fatcat:j74rx5lnqnfg5pimxmvh75rzem