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|C-reactive protein induces matrix metalloproteinase-1 and -10 in human endothelial cells: implications for clinical and subclinical atherosclerosis|
|Authors: ||Montero, I. (Inés)|
Orbe, J. (Josune)
Varo, N. (Nerea)
Beloqui, O. (Óscar)
Monreal, J.I. (José Ignacio)
Rodriguez, J.A. (José Antonio)
Diez, J. (Javier)
Libby, P. (Peter)
Paramo, J.A. (José Antonio)
Matrix Metalloproteinase 1/biosynthesis
|Issue Date: ||2006|
|Publisher version: ||http://www.sciencedirect.com/science/article/pii/S0735109706001513|
|Citation: ||Montero I, Orbe J, Varo N, Beloqui O, Monreal JI, Rodriguez JA, et al. C-reactive protein induces matrix metalloproteinase-1 and -10 in human endothelial cells: implications for clinical and subclinical atherosclerosis. J Am Coll Cardiol 2006 Apr 4;47(7):1369-1378.|
|OBJECTIVES: We examined the effect of C-reactive protein (CRP) on matrix metalloproteinase (MMP) and inhibitor expression in endothelial cells and in patients with clinical and subclinical atherosclerosis.
BACKGROUND: In addition to predicting atherosclerotic vascular disease, CRP may directly promote a proinflammatory/proatherosclerotic phenotype.
METHODS: Human umbilical vein endothelial cells (HUVECs) and aortic endothelial cells (HAECs) were incubated in the presence or absence of CRP (50 mug/ml). Microarray analysis, real-time polymerase chain reaction, immunological and activity assays for MMPs were performed. Specific inhibitors of mitogen-activated protein kinase pathway were used. The MMP-1 and -10 plasma levels were measured in apparently healthy subjects (n = 70). Immunolocalization of CRP, MMP-1, and MMP-10 was performed in human mammary arteries and carotid endarterectomy specimens.
RESULTS: C-reactive protein augmented MMP-1 and -10 messenger ribonucleic acid expression in HUVEC (p < 0.05) and HAEC (p < 0.01). C-reactive protein stimulation also increased MMP-1 and -10 protein in conditioned culture medium (p < 0.001), as well as MMP activity (p = 0.001). Specific inhibition of p38 or MEK abolished the CRP induction of the MMP-1, whereas MMP-10 induction blockade required the simultaneous inhibition of p38 and Jun N-terminal kinase pathways. Subjects with CRP values >3 mg/l (n = 37) had increased plasma MMP-1 and -10 (p < 0.05), the association being significant after adjustment for confounding variables (p = 0.04 and p = 0.008, respectively). The MMP-10 levels were elevated in subjects with higher carotid intima-media thickness (p = 0.009). Increased CRP and MMP-10 colocalized in endothelial layer and macrophage-rich areas in advanced atherosclerotic plaques.
CONCLUSIONS: Increased local and systemic CRP-related MMP activation might provide a link between inflammation and plaque vulnerability.|
|Permanent link: ||http://hdl.handle.net/10171/21870|
|Appears in Collections:||DA - CIMA - Cardiovasculares - Aterosclerosis e inflamación - Artículos de revista|
DA - CIMA - Cardiovasculares - Cardiopatía hipertensiva - Artículos de Revista
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