L. Gullestad et al., ANGIOTENSIN-II RECEPTOR SUBTYPE AT(1) AND AT(2) EXPRESSION AFTER HEART-TRANSPLANTATION, Cardiovascular Research, 38(2), 1998, pp. 340-347
Objective: Cardiac hypertrophy appears early after heart transplantati
on, and may represent a myocardial response to injury. Recent evidence
suggests that angiotensin II (Ang Ii) may promote growth through the
AT(1) and inhibit growth through the AT(2) receptor subtypes. We there
fore asked whether hypertrophy after heart transplantation is characte
rized by alterations in Ang II receptor gene expression. Methods: The
expression of Ang II receptor subtypes, AT(1) and AT(2), was analyzed
in right ventricular endomyocardial biopsies taken from 10 human donor
hearts prior to implantation (controls) and from 17 heart transplant
recipients, Il studied during annual evaluation (> 1 year after transp
lantation) and 6 one week after transplantation. Competitive reverse t
ranscription polymerase chain reaction (RT-PCR) was performed using sy
nthetic RNA internal standards for both receptor subtypes. Results: AT
(1) and AT(2) receptor mRNAs were detected in all samples. AT(1) recep
tor mRNA decreased 4.5 fold (p <0.01) and AT(2) receptor mRNA 4.2 fold
(p < 0.001) in transplant patients compared with controls. In the sub
group of patients examined one week after surgery AT(1) was reduced re
lative to AT(2) receptor mRNA, resulting in an altered ratio of AT(1)
to AT(2) early after transplantation, There was no correlation between
Ang II receptor levels and left ventricular wall thickness, and the d
ecrease in receptor level did not correlate with any hemodynamic param
eters, cyclosporine blood levels, or plasma renin, Ang II or pANP, exc
ept for a negative correlation between AT(2) mRNA and plasma renin (r
= - 0.49,p = 0.05). Conclusions: Contrary to our expectations, mRNA fo
r both Ang II receptors was downregulated after heart transplantation.
The cause of myocardial hypertrophy after heart transplantation is st
ill unclear, but the hypertrophy does not appear to be driven by incre
ased transcription of the AT(1) receptor. (C) 1998 Elsevier Science B.
V. All fights reserved.