Tesis doctoral de Ana Isabel Purroy López
We have investigated the role of metalloproteinase-10 (mmp-10) in the atherothrombotic process, using in vivo and in vitro experimental approaches, and explored its possible association with vascular calcification. aortic mmp-10 expression was observed in the atherosclerotic lesion of apolipoprotein e-/- (apoe-/-), but not in the healthy vascular wall of wild type mice, colocalizing with macrophage-like cells. In apoe-/- mice, lack of functional mmp-10 was associated with reduced lesion size in three different vascular beds, less vascular calcification, plaque rupture and macrophage content, and increased vascular smooth muscle cells, indicating a more stable plaque phenotype. we have also shown that mmp-10 is involved in human atherosclerosis: human atherosclerotic plaques express and secrete mmp-10 to the medium, particularly calcified atheromas. Circulating mmp-10 levels are associated with coronary calcium in subclinical atherosclerosis, a marker of cardiovascular risk. Chronic kidney disease patients present increased serum mmp-10 levels associated with the severity of atherosclerosis and vascular calcification. in vitro, mmp-10 accelerates endothelial wound healing by promoting human ecs migration and proliferation. Proinflammatory stimuli induce mmp-10 expression in endothelium, macrophages and vsmcs. Finally, we have demonstrated that while aortic vsmcs from mmp-10 deficient mice exhibit reduces calcium deposition, mmp-10 induces a calcifying phenotype in murine and human vsmcs. in summary, these findings reveal that mmp-10 plays a crucial role in different stages of the atherosclerotic process by promoting plaque inflammation and increased calcification. circulating mmp-10 concentration may represent a new risk marker of atherosclerosis, a predictor of cardiovascular events.
Datos académicos de la tesis doctoral «A prominent role of mmp-10 in atherosclerosis associated with vascular calcification«
- Título de la tesis: A prominent role of mmp-10 in atherosclerosis associated with vascular calcification
- Autor: Ana Isabel Purroy López
- Universidad: Navarra
- Fecha de lectura de la tesis: 21/12/2011
Dirección y tribunal
- Director de la tesis
- José Antonio Paramo Fernandez
- Tribunal
- Presidente del tribunal: Jesús De la osada García
- olivier gabriel Meilhac (vocal)
- Ana Fortuño gil (vocal)
- Fernando Civeira murillo (vocal)
