Extracellular matrix remodeling and matrix metalloproteinases in the vascular wall during aging and in pathological conditions.
The extracellular matrix provides a structural framework essential for the functional properties of vessel walls. The three dimensional organization of the extracellular matrix molecules - elastin, collagens, proteoglycans and structural glycoproteins - synthesized during fetal development - is optimal for these functions. In uninjured arteries and veins, some proteases are constitutively expressed, but through the control of their activation and/or their inhibition by inhibitors, these proteases have a very low activity and the turn-over of elastic and collagen fibers is low. During aging and during the occurrence of vascular pathologies, the balance between proteases and their inhibitors is temporally destroyed through the induction of matrix metalloproteinase gene expression, the activation of zymogens or the secretion of enzymes by inflammatory cells. Smooth muscle cells, the most numerous cells in vascular walls, have a high ability to respond to injury through their ability to synthesize extracellular matrix molecules and protease inhibitors. However, the three dimensional organization of the newly synthesized extracellular matrix is never functionally optimal. In some other pathologies - aneurysm - the injury overcomes the responsive capacity of smooth muscle cells and the quantity of extracellular matrix decreases. In conclusion, care should be taken to maintain the vascular extracellular matrix reserve and any therapeutic manipulation of the protease/inhibitor balance must be perfectly controlled, because an accumulation of abnormal extracellular matrix may have unforeseen adverse effects.
Jacob
Marie Paule
MP
Inserm U 460, Bâtiment 13, Hôpital Bichat-Claude Bernard, 46, rue Henri-Huchard, 75877 Paris cedex 18, France. jacob@bichat.inserm.fr
D000375:Aging / Q000473:pathology*; D000818:Animals; D005109:Extracellular Matrix / Q000201:enzymology / Q000473:pathology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology*; D011480:Protease Inhibitors / Q000494:pharmacology; D014652:Vascular Diseases / Q000201:enzymology / Q000473:pathology*
D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases