CONTRACTION OF FIBRILLAR TYPE-I COLLAGEN BY ENDOTHELIAL-CELLS - A STUDY IN-VITRO

The formation of microvascular sprouts during angiogenesis requires th at endothelial cells move through an extracellular matrix. Endothelial cells that migrate in vitro generate forces of traction that compress (i.e., contract) and reorganize vicinial extracellular matrix, a proc ess that might be important for angiogenic invasion and morphogenesis in vivo. To study potential relationships between traction and angioge nesis, we have measured the contraction of fibrillar type I collagen g els by endothelial cells in vitro. We found that the capacity of bovin e aortic endothelial (BAE) cells to remodel type I collagen was simila r to that of human dermal fibroblasts-a cell type that generates high levels of traction. Contraction of collagen by BAE cells was stimulate d by fetal bovine serum, human plasma-derived serum, bovine serum albu min, and the angiogenic factors phorbol myristate acetate and basic fi broblast growth factor (bFGF). In contrast, fibronectin and immunoglob ulin from bovine serum, several nonserum proteins, and polyvinyl pyrro lidone (a nonproteinaceous substitute for albumin in artificial plasma ) were not stimulatory. Contraction of collagen by BAE cells was dimin ished by an inhibitor of metalloproteinases (1,10-phenanthroline) at c oncentrations that were not obviously cytotoxic. Zymography of protein s secreted by BAE cells that had contracted collagen gels revealed mat rix metalloproteinase 2. Subconfluent BAE cells that were migratory an d proliferating were more effective contractors of collagen than were quiescent, confluent cells of the same strain. Moreover, bovine capill ary endothelial cells contracted collagen gels to a greater degree tha n was seen with BAE cells. Collectively, our observations indicate tha t traction-driven reorganization of fibrillar type I collagen by endot helial cells is sensitive to different mediators, some of which, e.g., bFGF, are known regulators of angiogenesis in vivo. (C) 1996 Wiley-Li ss, Inc.