Endothelial cell regulation by transforming growth factor‐beta

Pronounced changes including growth inhibition, increased matrix deposition and suppression of cell‐associated proteolytic activity, take place in endothelial cells (EC) upon the application of TGF‐β. Interrelationships between these effects have shed some light on the mechanism of action of TGF‐β and on its role in regulating EC function vis‐a‐vis angiogenesis. For instance, preliminary evidence has indicated that increased levels of certain matrix components may be partly responsible for the antiproliferative action of TGF‐β. In addition, TGF‐β and bFGF have opposing effects on cellular proteolytic balance which may contribute to the antagonistic effect that TGF‐β has on bFGF‐induced EC growth and possibly to the anti‐angiogenic effect exerted by TGF‐β under certain circumstances. Of particular interest in this regard is the fact that physical contact between EC and vascular mural cells in EC:mural cell cocultures has been found to generate active TGF‐β, thus further implicating TGF‐β in the maintenance of the quiescent, differentiated aggreation of EC as found in vascular structures in vivo. While more information is needed to define what, if any, role TGF‐β plays in endothelial differentiation, it is to be noted that many of the cellular and biochemical processes affected by TGF‐β are linked to differentiation. It is therefore possible that the growth inhibition of EC by TGF‐β primes them for differentiation and/or is critical for the maintenance of a differentiated state.