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Angiogenesis is the process of forming new blood vessels from existing blood vessels. It is a highly complex process involving extensive interplay between cells, soluble factors, and the extracellular matrix (ECM). Angiogenesis is critical during normal physiological development, but it also occurs in adults during inflammation, wound healing, ischemia, and in pathological conditions such as rheumatoid arthritis, hemangioma, and tumor growth. Proteolysis has been indicated as one of the first and most sustained activities involved in the formation of new blood vessels. Numerous proteases including matrix metalloproteases (MMPs), a disintegrin and metalloprotease domain (ADAM), a disintegrin and metalloprotease domain with throbospondin motifs (ADAMTS), and cysteine and serine proteases are involved in angiogenesis. This article focuses on the important and diverse roles that these proteases play in the regulation of angiogenesis. == MMPs == MMPs are a large multigene family of zinc-dependent endopeptidases. The collective MMP family is capable of degrading all known ECM macromolecules. MMP activity is regulated at the level of transcription, post-translationally by proteolytic cleavage, and by endogenous inhibitors known as tissue inhibitors of metalloproteases (TIMPs). The role of matrix metalloproteases and TIMPs in several pathological conditions including angiogenesis, tumor growth, and metastasis has been investigated and very well described. Matrix metalloproteases contain five conserved domains/sequence motifs: # Signal peptide sequence, which directs the enzyme into the rough endoplasmic reticulum during synthesis # Propeptide domain, which is cleaved to activate the enzyme # Catalytic domain, which contains the conserved Zn2+ binding region and mediates enzyme activity # Hemopexin domain, which provides the substrate specificity # Small hinge region, which allows the hemopexin domain to bring the substrate to the active core of the catalytic domain There is also a subfamily of the matrix metalloproteases, the membrane-type MMPs (MT-MMPs) which contain an additional transmembrane domain and a short cytoplasmic domain. After activation of MMPs by removal of the propeptide domain, their activity is regulated by TIMPs. TIMPs specifically and reversibly inhibit the activity of MMPs. So far there have been identified four members of the family, TIMP1–4. All TIMPs contain twelve conserved cystein residues, which form six disulfide bonds. The C-terminal domains of TIMPs are highly variable and confer their specificity towards preferred MMP targets. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Proteases in angiogenesis」の詳細全文を読む スポンサード リンク
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