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Matrix remodelling in dilated cardiomyopathy entails the occurrence of oncofetal fibronectin molecular variants
Objectives:
To investigate whether disturbance of the cellular homoeostasis and integrity of cardiomyocytes in dilated cardiomyopathy (DCM) is accompanied by alterations in cell-matrix relations as indicated by changes in the deposition of fibronectin (FN) isoforms.
Design:
Tissue from a case series of patients with DCM was investigated by immunohistochemistry with antibodies against FN (all variants, clone IST4), ED-A+ FN (clone IST9), ED-B+ FN (clone BC1), and oncofetal glycosylated FN (clone 5C10). The sites of de novo synthesis of FN were demonstrated by means of non-radioactive RNA in situ hybridisation (ISH) with biotinylated FN cDNA fragments as the probe.
Setting:
University hospital.
Patients:
Samples from 10 patients with clinical criteria and histological diagnosis of DCM and from 3 individuals with normal hearts.
Interventions:
Samples were obtained by right ventricular endomyocardial biopsy.
Main Outcome Measure:
Distribution of oncofetal FN variants in DCM hearts.
Results:
Immunostaining of FN (IST4, all variants) showed a coarse interstitial network in normal and diseased myocardium. ED-A+ FN was deposited as fine interstitial spots in normal myocardium and in DCM samples. Immunostaining for oncofetal glycosylated FN and ED-B+ FN was not seen in normal adult myocardium, whereas myocardium from DCM patients showed focal and delicate staining in the interstitium. RNA ISH showed that these deposits resulted from local FN synthesis.
Conclusion:
The results accord with de novo expression of oncofetal FN variants in hearts from patients with DCM. The oncofetal FN variants may serve as disease markers in myocardium affected by DCM.