Angiogenic and vascular modulation by extracellular matrix cleavage products.

In the last fifteen years different extracellular matrix proteins and cleavage products have been identified. These molecules possess the ability to regulate vascular development, repair and function. However, the concept is still inconsistent and only partially understood. In this review, we will focus on angiogenesis regulation by extracellular matrix processing. Therefore, possible regulatory mechanisms in vascular biology controlled by different cleavage products of basement membrane proteins (e.g. endostatin and tumstatin, endorepellin), their activation by proteases and inhibitors, such as matrix metalloproteases (MMPs), cathepsins, tissue inhibitors of MMPs and cystatin, will be reviewed. Up to now there is only limited knowledge about the situations, under which different ECM cleavage products will be released and produced by proteases. Beside vascular growth and the formation of new blood vessels, it is also important to pay attention to the implication of the mentioned proteins in the vascular repair process. Physical exercise and its angio-regulatory potentials have become in the focus in recent years. We will therefore discuss physical exercise and its effects on the mentioned molecules regarding angiogenic inductions. Until today it remains to be clearly stated, which impact might be achieved by matrix cleavage products with respect to the regulation of vascular progenitor cells and their possible therapeutical role in support of vascular repair mechanisms. Furthermore, the current knowledge of the functional role of ECM in the vascular system is highlighted.