Decreased expression of ventricular angiotensin receptor type 1 mRNA after human heart transplantation

Myocardial angiotensin receptors of type 1 (AT1) are downregulated at the protein and mRNA levels in human heart failure. No data are available for the transplanted human heart, which frequently exhibits functional alterations. The aim of the present study was the quantitation of ventricular AT1 mRNA content in endomyocardial biopsies from patients after heart transplantation. For the determination of AT1 mRNA we used a novel quantitative reverse transcription polymerase chain reaction with low variance (6%) based on an internal AT1 cRNA standard, liquid-phase hybridization of polymerase chain reaction products in microtiter plates, and quantitation by enzyme-linked immunosorbent assay. Right ventricular biopsies from 16 patients after heart transplantation (left ventricular ejection fraction 67 +/- 7%) were compared with 12 patients with normal cardiac function (left ventricular ejection fraction 62 +/- 5%). A 46% lower AT1 mRNA content was found in biopsies from the 16 patients after heart transplantation than in the 12 controls (heart transplantation, 200 +/- 25 AT1 mRNA copies/ng RNA; controls, 368 +/- 50; P < 0.01). When AT1 mRNA content was related to the stably expressed GAPDH mRNA, a 49% decrease was detected (AT1/GAPDH: patients, 2.4 +/- 0.25; controls, 4.7 +/- 0.6; P < 0.006). No association between the extent of AT1 downregulation and clinical or hemodynamic variables was detected. In the human heart ventricular AT1 is downregulated after orthotopic heart transplantation. The decrease in AT1 mRNA is not associated with altered systolic function. This may partially reflect a loss of autonomic nerves and thus altered nervous control of the heart.