It is proposed that insults such as proteolysis and wounding, or growth factor action, may provide the stimulus for basement membrane degradation or disruption; these events may induce quiescent EC to enter the second ECM phase and initiate the angiogenesis program (Figure 2, upper and lower left panels). In the case of proteases, it is widely held that MMPs, which comprise a family of at least 23 distinct endoproteinases, may be the likely players; their expression can be induced by growth factor or cytokine activity or through tissue injury. Significantly, more than half of the known MMPs have substrate specificities for one or more basement membrane components, and several of the pheno-types of mice null for specific MMPs include defective angiogenesis. Depending on the physiologic state of the vasculature, MMPs can be released by the EC or by perivascu-lar stromal or tumor cells. Moreover, the level of MMP activity would likely determine the outcome on angiogene-sis (i.e., low activities may cause limited release of antian-giogenic basement membrane fragments), but if disruption of the ECM scaffold is not significant enough to allow EC to breach the basement membrane, EC quiescence may be sustained. In contrast, high proteolytic activity would cause significant dissolution of the basement membrane, as well as promoting the release of factors, such as the heparin-binding FGFs or VEGFs sequestered by the various basement mem brane components, which would in turn stimulate the proliferative phase of angiogenesis. Notably, these and many others of the proangiogenic growth factors exhibit matrix-binding properties, and in some cases, require the function of cell surface or ECM proteoglycans as co-receptors for growth factor-receptor binding and activation. Although the role of proteases and growth factor action is likely crucial in promoting the progression of EC between the two ECM phases of angiogenesis, our review will not further examine these aspects because they are widely discussed elsewhere in the current literature and in this book.
Was this article helpful?
This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.