Human endothelial gelatinases and angiogenesis.
Endothelial cell invasion is an essential event during angiogenesis (formation of new blood vessels). The process involves the degradation of the basement membrane and the underlying interstitium. The matrix metalloproteinase (MMP) family is considered to be primarily responsible for matrix degradation. Two members of the family, gelatinase A and B play an important role in angiogenesis. This review outlines recent findings on their regulation in human endothelial cells. Latent gelatinase B is secreted from endothelial cells. This enzyme can also accumulate in the cytosol as an active enzyme, free of TIMP-1. In contrast, latent gelatinase A is constitutively secreted from the cells. Unlike other MMPs, gelatinase A activation occurs on the cell membrane and is mediated by MT1-MMP. A number of physiological activators have recently been described. These include thrombin and activated protein C, both of which activate gelatinase A independent of the MT1-MMP pathway. These new findings may lead to therapeutic interventions for the treatment of angiogenic-dependent diseases such as cancer and arthritis.
Nguyen
M
M
Sutton Arthritis Research Laboratory, Royal North Shore Hospital, New South Wales 2065, St. Leonards, Australia.
Arkell
J
J
Jackson
C J
CJ
D002462:Cell Membrane / Q000201:enzymology; D003094:Collagen / Q000378:metabolism* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D004792:Enzyme Precursors / Q000378:metabolism*; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology*; D018093:Gelatinases / Q000145:classification / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D019714:Tissue Inhibitor of Metalloproteinases / Q000145:classification / Q000235:genetics / Q000378:metabolism
D004792:Enzyme Precursors; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D018093:Gelatinases; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9