Endocardial endothelial celsl stimulate proliferation and collagen synthesis of cardiac fibroblasts |
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Authors: | Leena Kuruvilla Renuka R Nair Umashankar P R Arthur Vijayan Lal Chandrasekharan Cheranellore Kartha |
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Institution: | (1) Division of Cellular & Molecular Cardiology and Vivarium, Sree Chitra Tirunal Institute for Medical Sciences and Technology, 695011 Trivandrum, India |
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Abstract: | Given that vascular endothelial cells play an important role in the modulation of vascular structure and function, we hypothesized
that endocardial endothelial cells (EECs) may have a modulator role in regulating the cardiac interstitial cells. Endocardial
endothelial cells were isolated from freshly collected pig hearts and cardiac fibroblasts were isolated from 3- to 4-d-old
Wistar rats. Fibroblasts were cultured in the presence or absence of conditioned medium from EECs. Proliferation of cardiac
fibroblasts was measured by the incorporation of 3H]-Thymidine and collagen synthesis was assayed by the incorporation of 3H]-proline. To determine the involvement of signaling mediators, in separate experiments, cardiac fibroblasts were incubated
with BQ123 (selective ETA receptor antagonist), PD142893 (nonselective ETA/ETB receptor antagonist), Bis-indolylmaleimide (PKC inhibitor), PD 098059 (MEK inhibitor), or neutralizing anti-transforming
growth factor (TGF)-β-antibody. Endocardial endothelium-derived factors endothelin (ET)-1, TGF-β, and Angiotensin (Ang)-II
in the conditioned medium were assayed by enzyme-linked immunosorbent assay using commercially available kits. We report here
evidence that suggest that endocardial endothelial cells stimulate both proliferation and collagen synthesis of cardiac fibroblasts.
The response seems to be mediated by endothelin through its ETA receptor.
Our results also indicate that protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) pathways are essential for
the EEC-induced proliferation of cardiac fibroblasts. |
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Keywords: | Endocardium endothelium cardiac fibroblasts collagen endothelin transforming growth factor |
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