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It is generally accepted that aging of the vascular system plays an important role in cardiovascular disease (CVD). Recent experimental findings have indicated the involvement of the cytokine transforming growth factor-β1 (TGF-β1) in these vascular aging processes. This cytokine is, after binding to a cell receptor, associated with numerous cellular processes, including formation of the extracellular matrix (ECM, the biomolecular network that surrounds the cell). We implemented TGF-β1 signaling and its effect on ECM formation with piecewise-linear differential equations (PLDEs), which have several advantageous properties over traditional continuous modeling. Aging of the system was simulated as a reduction in cell sensitivity for TGF-β1. The model predicted a disturbed ECM balance during aging, which corresponds well to findings from the literature. The outcome of this hybrid approach was satisfactory and, therefore, we will continue modeling of various aging-related pathways with PLDEs in future research.
Date of Conference: 1-5 Sept. 2004