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- Title
Endocardial Endothelial Cells Stimulate Proliferation and Collagen Synthesis of Cardiac Fibroblasts.
- Authors
Leena Kuruvilla; Renuka R. Nair; P. R. Umashankar; Arthur Vijayan Lal; Chandrasekharan Cheranellore Kartha
- 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 cardiacinterstitial cells. Endocardial endothelial cells were isolated from freshly collected pig hearts and cardiacfibroblasts were isolated from 3- to 4-d-old Wistar rats. Fibroblasts were cultured in the presence or absence ofconditioned 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 involvementof signaling mediators, in separate experiments, cardiac fibroblasts were incubated with BQ123 (selectiveETA receptor antagonist), PD142893 (nonselective ETA/ETB receptor antagonist), Bis-indolylmaleimide (PKCinhibitor), 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 conditionedmedium were assayed by enzyme-linked immunosorbent assay using commercially available kits. We reporthere evidence that suggest that endocardial endothelial cells stimulate both proliferation and collagen synthesisof 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) pathwaysare essential for the EEC-induced proliferation of cardiac fibroblasts.
- Subjects
FIBROBLASTS; CONNECTIVE tissue cells; PROTEIN kinases; GROWTH factors
- Publication
Cell Biochemistry & Biophysics, 2007, Vol 47, Issue 1, p65
- ISSN
1085-9195
- Publication type
Article
- DOI
10.1385/CBB:47:1:65