Angiotensin receptor type 1 mRNA in human right ventricular endomyocardial biopsies: downregulation in heart failure

.Objective: Atrial angiotensin II receptors type 1 AT are downregulated in end-stage human heart failure at mRNA and protein1 level. The present study investigated whether AT ventricular mRNA content was reduced in myocardial biopsies from heart failure1 patients. Methods: AT mRNA was quantitated in right ventricular endomyocardial biopsies from 16 patients with decreased left1 . .ventricular function LVEF 36"3 % due to dilated cardiomyopathy DCM and in biopsies from 12 patients with suspected myocardial .disease but normal cardiac function LVEF 62"2 %. Two biopsies per patient were pooled, RNA was extracted and reverse-transcribed after addition of an AT cRNA standard. AT standard and wild-type RNA were amplified with the same primers in the same PCR tube.1 1 The PCR products were hybridized to a microtiter plate and detected and quantitated by an ELISA system. Glyceraldehyde phosphate .dehydrogenase GAPDH mRNA was determined in the same samples as AT mRNA. Results: In the biopsies from 16 patients with1 heart failure, a 68 % decrease in AT mRNA content was found in comparison with 12 controls heart failure 94"15 AT mRNA1 1.copiesrng RNA; controls 297"45; P-0.001. Relating AT mRNA content to GAPDH mRNA confirmed the specific decrease in AT1 1 .mRNA AT rGAPDH: heart failure 1.3"0.15; controls 3.4"0.5; P-0.002. The best correlation between AT mRNA content and1 1 .clinical parameters was found for right ventricular ejection fraction rs0.59, P-0.01. Conclusions: The quantitative RT-PCR procedure indicated a loss of ventricular AT mRNA in human heart failure which corresponds to the loss of AT protein described1 1 previously. It may underlie the decrease in AT protein expression in human heart failure.