Suppression of Human Microvascular Endothelial Cell Invasion and Morphogenesis With Synthetic Matrixin Inhibitors

摘要: Matrix metalloproteinases (MMPs, matrixins) are a family of zinc proteinases that digest extracellular matrix and play very important role in normal development pathological conditions such as cardiovascular diseases cancer metastasis. Type IV collagenases (gelatinase A/MMP-2 gelatinase B/MMP-9) may be critical the early steps angiogenesis, digestion basement membrane migration endothelial cells from existing blood vessels. Human dermal microvascular were cultured on type I collagen, reconstituted Matrigel differentiation was examined presence potent synthetic inhibitors MMPs. The thiol inhibitor MAG-283 had IC50 values 480 nM 3 against human interstitial collagenase (MMP-1) MMP-2, respectively, KI value 2.2 MMP-9. sulfodiimine YLL-224 180 nM, 63 44 MMP-1, -2, -9, respectively. These at low micromolar concentrations inhibited cell-mediated collagen degradation partially blocked cell invasion through collagen. also suppressed differentiation, i.e., formation capillary-like tubes results suggest collagen-degrading MMPs an during initiation angiogenesis.