Metalloproteinases and atherothrombosis: MMP-10 mediates vascular remodeling promoted by inflammatory stimuli.
Atherosclerosis is the common pathophysiological substrate of ischemic vascular diseases and their thrombotic complications. The unbalance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) has been hypothesized to be involved in the growth, destabilization, and eventual rupture of atherosclerotic lesions. Different MMPs have been assigned relevant roles in the pathology of vascular diseases and MMP-10 (stromelysin-2) has been involved in vascular development and atherogenesis. This article examines the pathophysiological role of MMPs, particularly MMP-10, in the onset and progression of vascular diseases and their regulation by pro-inflammatory stimuli. MMP-10 over-expression has been shown to compromise vascular integrity and it has been associated with aortic aneurysms. MMP-10 is induced by C-reactive protein in endothelial cells, and it is over-expressed in atherosclerotic lesions. Additionally, higher MMP-10 serum levels are associated with inflammatory markers, increased carotid intima-media thickness and the presence of atherosclerotic plaques. We have cloned the promoter region of the MMP-10 gene and studied the effect of inflammatory stimuli on MMP-10 transcriptional regulation, providing evidences further supporting the involvement of MMP-10 in the pathophysiology of atherothrombosis.
Rodriguez
Jose A
JA
Atherosclerosis Research Laboratory, Division of Cardiovascular Sciences. CIMA-University of Navarra. Avda. Pio XII 55, 31008 Pamplona, Spain. josean@unav.es
Orbe
Josune
J
Martinez de Lizarrondo
Sara
S
Calvayrac
Olivier
O
Rodriguez
Cristina
C
Martinez-Gonzalez
Jose
J
Paramo
Jose A
JA
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D002319:Cardiovascular System; D004730:Endothelium, Vascular / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007249:Inflammation; D053506:Matrix Metalloproteinase 10 / Q000378:metabolism*; D045726:Metalloproteases / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D013927:Thrombosis / Q000201:enzymology / Q000378:metabolism*; D014158:Transcription, Genetic
D015415:Biomarkers; D045726:Metalloproteases; D053506:Matrix Metalloproteinase 10