Angiogenesis and the Fibrinolytic System

Abstract

Angiogenesis is defined as the formation of capillaries from preexisting blood vessels. This involves a balanced spatiotemporal modulation of endothelial cell adhesion, migration, and proliferation. An array of proteolytic enzymes expressed from endothelial cells including those of the plasminogen activator/plasmin system are required for angiogenesis to occur. In this review we focus on the growth factors that are involved in the angiogenic process and that modulate the expression and/or the activity of the plasminogen activator/plasmin system. The elucidation of the interactions between angiogenic growth factors, endothelial cell proteolytic enzymes, and the extracellular environment could ultimately lead to the therapeutic approaches to block angiogenesis and the pathophysiological conditions associated with it.

Expression of Tissue Inhibitor of Metalloproteinase-4 in Normal Human Corneal Cells and Experimental Corneal Neovascularization

“…On the other hand, the implications of MMP/TIMP expressed by cells other than vascular endothelial cells in the cornea during the angiogenic process require elucidation. From this and previous studies, we hypothesized that increased rather than decreased total TIMP activity in the corneal tissue may offer a tight control over the increased MMP activity during the angiogenic process, so that the corneal stroma becomes more permissive for vascular ingrowth, yet not too destructive, as in the case of corneal ulcer and melting due to excessive MMP activity, which is detrimental to vessel growth [17,19,39,40].…”

Spontaneous development of otitis media in plasminogen-deficient mice

“…A main function of the PA system is to degrade fibrin during thrombolysis (Bugge et al, 1995a;Vassalli et al, 1991). The PA system may also play an important role in a variety of other physiological and pathological processes such as angiogenesis (Pintucci et al, 1996), tumor invasion (Andreasen et al, 1997), brain damage (Gingrich and Traynelis, 2000) and skin wound healing (Romer et al, 1996). However, recent studies also indicate that pathogenic bacteria use the PA system to increase their invasiveness and enhance their ability to cross tissue barriers (Boyle and Lottenberg, 1997;Goguen et al, 2000;Nordstrand et al, 2001).…”

Angiomotin expression promotes hemangioendothelioma invasion

“…Cell migration and invasion are fundamental components of tumor cell invasion and neovascularization. The activation of matrix metalloproteinases (MMPs) is essential for cells to migrate through extracellular matrix (Pepper et al, 1996;Pintucci et al, 1996). In order to analyse MMP activation, conditioned media from equivalent numbers of MAE-Amot, Amot or vector control cells were collected.…”