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Título: Extracellular matrix metabolism in injury-induced atherosclerosis
Autores: Wang, He, 1965-
Fecha: 1996
Publicador: McGill University - MCGILL
Fuente:
Tipo: Electronic Thesis or Dissertation
Tema: Biology, Molecular.
Health Sciences, Pathology.
Descripción: Remodelling of extracellular matrix (ECM) is a prominent feature of atherosclerotic lesions and contributes to lipoprotein retention as well as smooth muscle cell (SMC) activation. To gain further knowledge about ECM, certain ECM components and their degrading enzymes were studied in injury-induced arterial neointima, which shares features with early atherosclerotic lesions.
It has been shown that synthesis of collagen and syndecan-1, a hybrid heparan/chondroitin sulfate proteoglycan, is enhanced. In situ hybridization indicates that syndecan positive cells are restricted to the arterial neointima. These data confirm the importance of arterial SMC in ECM metabolism and indicate that increased synthesis contributes to ECM accumulation in neointima.
Remodelling of ECM in atherogenesis refers not only to increased ECM deposition, but also involves enhanced ECM catabolism. A family of zinc-containing proteinases, termed matrix metalloproteinases (MMPs) has recently been implicated in atherosclerosis. Subsequently, we examined expression of two common MMPs, MMP-2 and MMP-9 in our model. The mRNAs for both MMPs are up-regulated, but their tissue distribution is different: MMP-2 positive cells are visible in neointima and in aortic media; whereas cells positive for MMP-9 are located only in neointima. MMPs are active at neutral pH and in tissue, their activity is regulated by tissue inhibitors of metalloproteinases (TIMPs) including TIMP-1. The enhanced MMP expression in neointima makes it relevant to examine the simultaneous expression of TIMP-1. To do this, we cloned rabbit TIMP-1 from neointima using a PCR-cloning technique. Transformation of the cloned gene resulted in synthesis of a TIMP-1 protein in E. Coli. The concentration of TIMP-1 in neointima was examined and a significant increase of both mRNA and protein levels was observed. It is suggested that the proteolytic activity of MMPs contributes to ECM breakdown. However, this digestion is limited, as continuous augmentation of TIMP-1 expression is observed after aortic de-endothelialization.
Idioma: en