[Matrix metalloproteinases and atherosclerosis. Therapeutic aspects].
Matrix metalloproteinases (MMPs) play a key role in the physiology of connective tissue development, morphogenesis and wound healing, but their unregulated activity has been implicated in numerous disease processes including arthritis, tumor cell metastasis and atherosclerosis. MMP family consists of at least 20 members; MMPs are produced by the different cell types (vascular smooth muscle cells, monocytes, endothelial cells) involved in the atheromatous plaque formation and participate to extracellular matrix remodelling and cell infiltration or migration. Since excessive tissue remodelling and increased matrix metalloproteinase activity have been demonstrated during atherosclerotic lesion progression (including plaque disruption), MMPs represent a potential target for therapeutic intervention to modify vascular pathology, by restoring the MMP/TIMP physiological equilibrium. This review highlights the structures of MMPs and their physiological inhibitors, the Tissue Inhibitors of MMPs (TIMPs), and describes the current developments in pharmacological MMP inhibition.
Beaudeux
J-L
JL
Service de biochimie C, Group hospitalier Pitié-Salpêtrière, AP-HP, 47-83 boulevard de l'hôpital, 75651 Paris cedex 13. jean-louis.beaudeux@psl.ap-hop-paris.fr
Giral
P
P
Bruckert
E
E
Foglietti
M-J
MJ
Chapman
M J
MJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001018:Aortic Diseases / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000517:prevention & control; D016022:Case-Control Studies; D002986:Clinical Trials as Topic; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D004318:Doxycycline / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000150:complications; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000097:blood / Q000235:genetics / Q000502:physiology*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D009930:Organic Chemicals; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D051381:Rats; D012307:Risk Factors; D013876:Thiophenes / Q000627:therapeutic use; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000502:physiology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000502:physiology; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000097:blood / Q000502:physiology; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D000960:Hypolipidemic Agents; D061965:Matrix Metalloproteinase Inhibitors; D009930:Organic Chemicals; D013876:Thiophenes; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; C113282:prinomastat; D019716:Tissue Inhibitor of Metalloproteinase-2; D010649:Phenylalanine; C080985:batimastat; C100342:marimastat; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases; D004318:Doxycycline
Métalloprotéases matricielles et athérosclérose. Perspectives thérapeutiques.