Reduced beta 1 receptor messenger RNA abundance in the failing human heart.

摘要: Heart failure in humans is characterized by alterations myocardial adrenergic signal transduction, the most prominent of which down-regulation beta 1-adrenergic receptors. We tested hypothesis that receptors failing human heart related to decreased steady-state levels 1 receptor mRNA. Due extremely low abundance mRNA, measurements were possible only quantitative polymerase chain reaction (QPCR) or RNase protection methods. Because gene intronless and mRNA low, QPCR yielded genomic amplification total RNA, had be performed poly (A)(+)-enriched RNA. By concentration varied from 0.34 7.8 x 10(7) molecules/microgram poly(A)(+)-enriched assay was sensitive 16.7 zeptomol. Using 100-mg aliquots left ventricular myocardium obtained organ donors (nonfailing ventricles, n = 12) transplant recipients (failing 13), respective measured 4.2 +/- 0.7 10(7)/micrograms vs. 2.10 0.3 (P 0.006). In these same nonfailing ventricles densities 67.9 6.9 fmol/mg 29.6 3.5 0.0001). Decreased confirmed assays also demonstrated a 50% reduction message abundance. conclude contributes heart.