ANGIOTENSIN RECEPTOR-TYPE-1 MESSENGER-RNA IN HUMAN RIGHT-VENTRICULAR ENDOMYOCARDIAL BIOPSIES - DOWN-REGULATION IN HEART-FAILURE

Objective: Atrial angiotensin II receptors type 1 (AT(1)) are downregu lated in end-stage human heart failure at mRNA and protein level. The present study investigated whether AT(1) ventricular mRNA content was reduced in myocardial biopsies from heart failure patients. Methods: A T(1) mRNA was quantitated in right ventricular endomyocardial biopsies from 16 patients with decreased left ventricular function (LVEF 36 +/ - 3%) due to dilated cardiomyopathy (DCM) and in biopsies from 12 pati ents with suspected myocardial disease but normal cardiac function (LV EF 62 +/- 2%). Two biopsies per patient were pooled, RNA was extracted and reverse-transcribed after addition of an AT(1) cRNA standard. AT( 1) standard and wild-type RNA were amplified with the same primers in the same PCR tube. The PCR products were hybridized to a microtiter pl ate and detected and quantitated by an ELISA system. Glyceraldehyde ph osphate dehydrogenase (GAPDH) mRNA was determined in the same samples as AT(1) mRNA. Results: In the biopsies from 16 patients with heart fa ilure, a 68% decrease in AT(1) mRNA content was found in comparison wi th 12 controls (heart failure 94 +/- 15 AT(1) mRNA copies/ng RNA; cont rols 297 +/- 45; P < 0.001). Relating AT(1) mRNA content to GAPDH mRNA confirmed the specific decrease in AT(1) mRNA (AT(1)/GAPDH: heart fai lure 1.3 +/- 0.15; controls 3.4 +/- 0.5; P < 0.002). The best correlat ion between AT(1) mRNA content and clinical parameters was found for r ight ventricular ejection fraction (r = 0.59, P < 0.01). Conclusions: The quantitative RT-PCR procedure indicated a loss of ventricular AT(1 ) mRNA in human heart failure which corresponds to the loss of AT(1) p rotein described previously. It may underlie the decrease in AT(1) pro tein expression in human heart failure.