Alterations induced by cyclosporine A in myocardial fibers and extracellular matrix in rat
R. Rezzani, P. Angoscini, L. Rodella and R. Bianchi
Division of Human Anatomy, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy
Offprint requests to: Prof. Rossella Bianchi, Division of Human Anatomy, Department of Biomedical Sciences and Biotechnology, Via Valsabbina 19, 25123 Brescia, Italy. Fax: +39-30-3717409. e-mail: bianchi@med.unibs.it
Summary. Cyclosporine A (CsA) is the first choice immunosuppressant
universally used in allo-transplantation. However, it has been
demonstrated that this drug produces unwanted side effects in
several organs and in particular in the kidney and in the heart.
While the cardiac toxicity, due to alteration of myocardial prostanoid
has been reported, no data are available about the effects of
CsA on myocardial cytoarchitecture. We studied the CsA induced
alterations of the myocardial structure and of the extracellular
matrix components (ECM). To test the ECM enzymatic changes we
studied a family of enzymes (matrix metalloproteinase-MMP), responsible
for the degradation of extracellular matrix components. In particular
we investigated MMP1, MMP2 and MMP9.
The study was carried out on two groups of Wistar rats. The group
I animals served as a control and were injected subcutaneously
daily with castor oil for 21 days. Group II: animals were subcutaneously
injected daily with CsA (dose: 15 mg/Kg in castor oil) for 21
days. The group I animals (control) had normal heart architecture
and low levels of MMP1, MMP2 and MMP9. The group II animals showed
degenerative changes with myocardial fibrosis, low levels of MMP1
and MMP9 but a clear increase in MMP2.
We suggest that the myocardial fibrosis was a consequence of the
cardiotoxic effect of CsA determining the alteration of the balance
between synthesis and degradation of ECM. The increase in MMP2
suggests that this enzyme could play a protective role during
myocardial damage and represent a compensatory mechanism for the
excessive accumulation of collagen. Histol. Histopathol. 17,
761-766 (2002)
Key words: Cyclosporine A, Heart, Rat, Matrix-metalloproteinases
DOI: 10.14670/HH-17.761