Extracellular matrix remodeling in the vascular wall

The extracellular matrix provides a structural framework essential for the functional properties of Vessel walls. The three dimensional organization o f the extracellular matrix molecules - elastin, collagens, proteoglycans an d structural glycoproteins - synthesized during fetal development - is opti mal for these functions. Early in life, the Vessel wall is subjected to inj ury: lipid deposition, hypoxia, enzyme secretion and reactive oxygen specie s production during inflammatory processes, and the extracellular matrix mo lecules are hydrolyzed by proteases - matrix metalloproteinases, leukocyte elastase, etc. In uninjured arteries and veins, some proteases are constitu tively expressed, hut through the control of their activation and/or their inhibition by inhibitors, these proteases have a very Low activity. During the occurrence of vascular pathologies - atherosclerosis, hypertension, var icosis, restenosis, etc. - the balance between proteases and their inhibito rs is temporally destroyed through the induction of matrix metalloproteinas e gene expression or the secretion of enzymes by inflammatory cells. Smooth muscle cells, the most numerous cells in vascular walls, have a high abili ty to respond to injury through their ability to synthesize extracellular m atrix molecules and protease inhibitors. However, the three dimensional org anization of the newly synthesized extracellular matrix is never functional ly optimal. In some other pathologies - aneurysm - the injury overcomes the responsive capacity of smooth muscle cells and the quantity of extracellul ar matrix decreases. In conclusion, care should be taken to maintain the va scular extracellular matrix reserve and any therapeutic manipulation of the protease/inhibitor balance must be perfectly controlled, because an accumu lation of abnormal extracellular matrix may have unforeseen adverse effects . (C) 2001 Editions scientifiques et medicales Elsevier SAS.