Nephrology Dialysis Transplantation, Vol 13, Issue 8 1958-1966, Copyright © 1998 by Oxford University Press
K Amann, G Kronenberg, F Gehlen, S Wessels, S Orth, K Munter, H Ehmke, G Mall and E Ritz
Background. In view of the high rate of cardiac death
in renal failure, the factors involved in the genesis of structural changes
in the heart are of obvious interest. The present study addresses the issue
whether growth factors known to be involved in cardiac remodelling are
abnormally expressed in rats with renal failure.
Methods. Sprague-Dawley rats were subjected to
binephrectomy (2 days) or subtotal nephrectomy (8 weeks). Controls were
sham-operated rats and rats with Goldblatt hypertension. Cardiac expression
of proliferating cellular nuclear antigen (PCNA), of growth factors and of
their receptors (PDGF, TGF-{beta}, VEGF) was investigated
immunohistochemically. In addition, cardiac PDGF- and TGF-{beta} mRNA
were assessed using quantitative RT-PCR. Results.
Eight weeks after subtotal nephrectomy (SNX) significantly increased
expression of PCNA and PDGF was found in the cardiac interstitium and of
PCNA and VEGF in the walls of intramyocardial arteries. In addition,
PCNA-positive cardiomyocytes were noted in SNX. Similar changes were not
seen in the hearts of hypertensive controls, i.e. rats with renovascular
hypertension, despite slightly higher blood pressure and more pronounced
left ventricular hypertrophy (LVH). While significant changes of cardiac
PDGF- and TGF-{beta} mRNA expression could not be documented in the
whole-heart homogenates 8 weeks after subtotal nephrectomy, 2 days after
bilateral nephrectomy PDGF mRNA was significantly increased and
TGF-{beta} mRNA decreased. Conclusion. The
observations demonstrate (i) specific activation of cardiac interstitial
cells after SNX, (ii) activation of postmitotic cardiomyocytes, possibly
predisposing to apoptosis, (iii) increased expression of PDGF in the
cardiac interstitium and in the wall of intramyocardial arteries, (iv)
increased expression of VEGF associated with hypertrophy of arterial smooth
muscle cells. These results were not explained by elevated blood pressure
or LVH, respectively. Keywords: experimental renal
failure; myocardium; remodelling; PCNA; growth factors
ORIGINAL ARTICLES
Cardiac remodelling in experimental renal failure - an immunohistochemical study
Departments of Pathology, Internal Medicine, Physiology, University of Heidelberg, Heidelberg, Germany; Department of Pathology, Darmstadt, Germany; Knoll AG, Ludwigshafen, Germany; Correspondence to: K Amann, Department of Pathology, Im Neuenheimer Feld 220, D-69120 Heidelberg, Germany
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