title: Analysis of the transforming growth factor-beta/sub 1/ pathway and extracellular matrix formation as a hybrid system.
abstract: 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-beta/sub 1/ (TGF-beta/sub 1/) 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-beta/sub 1/ 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-beta/sub 1/. 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.
authors.affiliation: Dept. of Electr. Eng., Eindhoven Univ. of Technol., Netherlands.
authors.forename: M W J M
authors.initials: MW
authors.lastname: Musters
authors.forename: N A
authors.initials: NA
authors.lastname: van Riel