Flow induced shear stress belongs to mechanical forces which play a significant role in controlling the vasculature. Acutely shear stress may be understood as the control variable for local diameter regulation by autacoids like nitric oxide (NO). However, if flow changes are persistent shear stress may be elevated chronically and adaptive remodeling processes of the vessel wall are induced in a long term range. Those adaptations like changes in wall thickness and new vessel formation are dependent on fine tuned signals composed mainly by changes in gene expression, release of growth factors, and degradation of extra cellular matrix. All those processes have been shown to be directly induced by shear stress. The exact mechanism translating a mechanical force into an cellular biochemical signal, however, is still only partly understood and it is hypothesized that cell-matrix interactions may be involved. To study the direct effect of cellular matrix binding on shear stress dependent eNOS-expression endothelial cells (EC) grown on different matrix components were subjected to shear stress in vitro. Only when they are seeded on a laminin containing matrix they responded to shear stress with a 2fold increase of the eNOS mRNA expression. This eNOS-mRNA increase could be prevented by an inhibition of cellular laminin binding with the peptide YIGSR. This peptide represents a sub-sequence of the β 1 chain of laminin which is bound by a laminin receptor (LBP) of 67kDa. The shear stress dependent alterations of eNOS expression are due to an increased transcription no increase was found during incubation with actinomycin D. Similar to the eNOS mRNA western blots against eNOS protein showed elevated values only when the cells were grown on laminin. As for the mRNA the elevation of eNOS-protein could be prevented by inhibition of LBP with YIGSR. Western blots showed that the expression of the LBP itself appeared to be up-regulated by shear stress indicating a feedback loop mechanism. Beside these non-integrin matrix receptor-effects we could show that EC exposed to elevated shear stress release bFGF a cytokine stored in large amounts within the cells. We could further show that this release is not due to unspecific cell damage but rather be part of a regulated pathway involving the integrin αvβ3 and indicating again a participation of cell matrix interactions in sensing shear stress. Basic FGF regulates EC proliferation/migration and angiogenesis and therefore may participate in vascular remodeling. Due to its lack of a signal sequence it is evident that bFGF is not secreted via the classical vesicular pathway of the golgi. It was shown earlier that small heat shock protein, hsp27, and bFGF are co-expressed in EC and that enhanced expression of hsp27 facilitates release of bFGF. Based on our hypothesis that shear stress induced bFGF release is controlled by cell-matrix interaction we investigated whether matrix modulation by proteases contribute to the signaling cascade in bFGF release and studied the role of hsp27 in this process. In conditioned media of EC subjected to shear stress a 3-fold enhanced elastase activity was found together with a 10-fold higher bFGF release. This bFGF release was significantly reduced by protease inhibition. Moreover, static cells treated with elastase demonstrated a similarly increased bFGF release. As shown earlier for shear stress this elastase induced bFGF release could be prevented by inhibition of integrin αvβ3. Furthermore, like in shear stress hsp27 was phosphorylated upon elastase treatment which could be prevented by both, inhibition of integrin αvβ3 and p38 MAP Kinase. Finally, co-precipitation experiments indicated a close physical interaction of bFGF with phosphorylated hsp27. These results indicate that the mechanism of shear stress induced bFGF release is critically dependent on matrix modulation via proteases (elastase) which might subsequently alter specific cell-matrix interactions via certain integrins (here αvβ3). We further investigated whether matrix fragments generated by elastase would have specific own effects on EC and might contribute to vascular remodeling. EC subjected to shear stress exhibited enhanced elastase activity in conditioned media. This went along with an increased occurrence of the laminin fragment E8 within the matrix. EC seeded on purified E8 resulted in a reduced proliferation and exhibited a 2-fold higher apoptosis rate as well as an increased O2- production. Aortic ring sprouting was significantly inhibited by E8. This inhibition was revoked by application of radical scavengers. These results indicate that during shear stress the matrix is altered proteolytically, a mechanism which might be part of a feed back loop to limit shear stress induced proliferation and differentiation of EC in adaptive vascular remodeling to increased flow.