Gene expression profile of mouse myocardium with transgenic overexpression of A₁ adenosine receptors

Transgenic mice with cardiac-specific overexpression of adenosine A ₁ receptors (A₁AR) have demonstrated metabolic and functional tolerance to myocardial ischemia. We utilized cDNA microarrays to test the hypothesis that the cardioprotective mechanism(s) of A₁ overexpression involves altered gene expression. Total RNA extracted from the left ventricles from A₁ transgenic (n = 4) and wild-type (n = 6) mice was hybridized to Affymetrix mgU74A chips. Comparison of RNA expression levels in transgenic to wild-type myocardium revealed ∼636 known genes with expression significantly altered by greater than 25%. We observed increased expressions of genes including NADH dehydrogenase, the GLUT4 glucose transporter, Na-K-ATPase, sarcolemmal K_ATP channels, and Bcl-xl in A₁AR-overexpressing hearts. We also observed decreased expression of pro-apoptotic genes including a 50% reduction in message level of caspase-8. Protein expression of GLUT4 and caspase-8 was also altered comparable to the differences in gene expression. These data illustrate genes with chronically altered patterns of expression in A₁ transgenic mouse myocardium that may be related to adenosine receptor overexpression-mediated cardioprotection.