Differential Expression of Matrix Metalloproteinases and Tissue Inhibitors and Extracellular Matrix Remodeling in Aortic Regurgitant Hearts
ABSTRACT Myocardial fibrosis in experimental aortic regurgitation (AR) features abnormal fibronectin with normal collagen content, but the relevant degradative processes have not been assessed.
To elucidate these degradative processes, mRNA (Northern) and protein levels (Western) of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), as well as MMP activity (zymography), were measured in cardiac fibroblasts (CF) from New Zealand white rabbits with experimental AR paired with normals (NL). Collagen and fibronectin were quantified by immunohistochemical staining.
In AR CF versus NL CF, MMP-2 and -14 mRNA and protein were increased (both p < 0.005), while TIMPs 1-3 were slightly decreased (p < 0.05-0.005; TIMP-4 undetectable). Gelatinase activity in AR CF was 1.7 times that in NL CF (p < 0.005); fibronectinase activity was unaffected. The Jun N-terminal kinase (JNK) inhibitor SP600125 suppressed MMP-2 protein (0.4-fold, p < 0.05) and mRNA (0.7-fold, p < 0.005) in AR CF; MMP-2 levels in NL CF were unaffected. AR MMP-9 mRNA, protein and activity were low and indistinguishable from NL. In left ventricular tissue, fibronectin was increased 1.9-fold (AR vs. NL, p < 0.05). Total AR collagen was indistinguishable from NL, but the collagen III to collagen I isoform ratio decreased (0.4-fold, p < 0.05).
Collagen is relatively deficient in AR fibrosis, due at least in part to upregulated MMPs and downregulated TIMPs; fibronectinase is unaltered. JNK-dependent regulation may stimulate both MMP-2 and fibronectin expression in AR, providing a potential therapeutic target.
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ABSTRACT: Actual interconnected power systems are very large structures which suffer from a large gap between electricity demand and generation and from an inadequate transmission capacity of interconnection lines. In such systems, blackouts have become an all too common an occurrence. This paper proposes a method to reinforce the power systems by insertion of FACTS (flexible alternating current transmission system) devices, which are optimal placed in order to eliminate the dangerous contingencies of the systems and to prevent by this way the apparition of blackout if outages occurs. The FACTS devices are optimal placed in order to maximizing the power system security, the optimization is carried out using three parameters: the location of FACTS devices, their type and their sizes. For this purpose we developed a hybrid software based on GAs (genetic algorithms), which uses Matlabtrade and the EUROSTAGtrade software for load flow calculations. The proposed procedures are successfully tested on an IEEE 14-bus power systemFuture Power Systems, 2005 International Conference on; 12/2005
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