Cyclic mechanical load and growth factors stimulate endothelial and smooth muscle cell DNA synthesis

Under nonpathologic conditions, endothelial cells (EC) and smooth muscle cells (SMC) maintain a low division rate. However, when a pathologic state occurs such as in clot formation, an angioplasty-induced wound or atherosclerosis, cellular equilibrium is disturbed and cell division may be driven by both mechanical loading and activity of exogenous and endogenous growth factors. We have utilized an in vitro model of dynamic culture to test the mitogenic responses of vascular cells to mechanical load and growth factors. Target cells were grown to confluence and quiescence on collagen type I bonded, silicone rubber membranes, subjected to 0.24 or 0.27 maximum strain, 1 Hz load regimes using a Flexercell® Strain Unit for 24 h or 3 days with or without added growth factors and the mitogenic responses quantitated after ³H-thymidine incorporation. EC responded mitogenically to cyclic load in a threshold manner beginning at approximately 15-18% elongation. SMC did not respond to applied load by synthesizing DNA unless load was accompanied by the presence of a growth factor. Growth factors (platelet derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I)) increased SMC DNA synthesis in decreasing magnitude in the following order: load + PDGF bb + IGF-I > PDGF bb + IGF-I >load + IGF-I >IGF-I alone (p<0.01). The normally low rate of cell division in EC and SMC can be upregulated by applied mechanical load in vitro in EC, and requires a growth factor(s) and load to stimulate cell division in SMC.