Fibrosis of the left atria during progression of heart failure is associated with increased matrix metalloproteinases in the rat

AbstractObjectivesThe purpose of this study was to determine the pathogenic factors and molecular mechanisms involved in fibrosis of the atria.BackgroundFibrosis is an important component of the pathophysiology of atrial fibrillation, especially when the arrhythmia is associated with heart failure (HF) or atrial dilation.MethodsWe used a rat model of myocardial infarction (MI) complicated by various degrees of left ventricular dysfunction and atrial dilation to study fibrosis and matrix metalloproteinase (MMP) activity in the left atrial (LA) myocardium by means of histologic, Western blot, zymographic, and immunohistologic techniques.ResultsThree months after surgical ligature of the left coronary artery, 27 rats had a large MI, 12 were in mild HF, and 15 in severe HF. Both groups had LA enlargement at the echocardiography. Masson’s trichrome and picrosirius staining of tissue sections revealed marked fibrosis at the periphery of trabeculae and also surrounding myolytic myocytes, in both mild and severe HF. In mild HF, the activity and expression of the matrilysin MMP-7 were increased (122%), whereas in severe HF, both MMP-7 (211%) and the gelatinase MMP-2 (187%) were up-regulated. There were no changes in the expression or activity of MMP inhibitors, TIMP-1, -2, and -4. Immunostaining of cryosections showed that MMP-2 was present in the interstitial spaces, whereas MMP-7 accumulated in myolytic myocytes.ConclusionsHemodynamic overload of the atria is an important pathogenic factor of fibrosis; MMP-7 appears to be involved in the early stage of this tissue remodeling process

Taking advantage of architectural diversity to improve control of splash dispersed disease in cultivar mixtures : a modelling study based on field experimentation

oral communication abstractUsing cultivar mixtures, i.e. growing several cultivars with different resistance traits in a same field, allows protection of susceptible cultivars and fungicide use reduction. Protective mixture effect against splash dispersed diseases such as septoria tritici blotch is variable depending on environmental conditions. Understanding disease reduction mechanisms is critical for improvement of mixture design and efficiency. Major mechanisms are related to modification of disease dispersal patterns within the mixture. Increased distance between two susceptible plants reduces spore transfer, while the presence of resistant plants provides a barrier to spore dispersal. Common mixture design recommendations include choice of cultivars with similar architecture in order to constitute homogeneous canopies which should minimize competition and ease agronomical management. However, no information is available on the possible impact of mixing cultivars with contrasted architecture on disease dispersal. We used a mechanistic modelling approach based on experimental results to characterize splash dispersal patterns in wheat cultivar mixtures with either uniform (homogeneous canopies) or contrasted straw height (heterogeneous canopies). We then performed numerical experiments to study the impact of variations in location of susceptible and resistant tissues within the canopy. Dispersal events were simulated based on field observations. Chosen rain dispersal events occurred during the post-flowering phase of wheat cycle, where disease develops on top leaves and reduces yield. At this stage, canopy structure is fully developed and fixed. Architectural measurements of individual plants were used to reconstruct static 3D mockups of pure stands and mixed canopies. Mockups provided information on resistant and susceptible tissue location within the canopies and were used to compute splash dispersal. Model inputs also included leaf disease severity and rain characteristics measured during studied dispersal events. Simulated spore dispersal was consistent with spore fluxes measured in the field. Disease reduction mechanisms that are specific to heterogeneous canopies were identified. Upper leaves of the tall cultivar acted as umbrellas by intercepting raindrops and reducing splash on diseased leaves at the bottom of the canopy. On the other hand, contaminated splash droplets produced at the same location were trapped by leaves of the lowest cultivar, thus reducing contamination of upper leaves of the tallest cultivar. Modelling results allowed quantification and hierarchisation of dispersal processes occurring in heterogeneous mixed canopies and outlined the importance of the location of resistant and susceptible organs within the canopy

Photoinduced Arylation of Acridinium Salts: Tunable Photoredox Catalysts for C-O Bond Cleavage

International audienceA photoinduced arylation of N-substituted acridinium salts has been developed and has exhibited a high functional group tolerance (e.g., halogen, nitrile, ketone, ester, and nitro). A broad range of well-decorated C9-arylated acridinium-based catalysts with fine-tuned photophysical and photochemical properties, namely, excited-state lifetimes and redox potentials have been synthetized in a one-step procedure. These functionalized acridinium salts were later evaluated in the photoredox-catalyzed fragmentation of 1,2-diol derivatives (lignin models). Among them, 2-bromophenyl substituted N-methyl acridinium has outperformed all photoredox catalysts, including commercial Fukuzumi’s catalyst, for the selective C(β)O-Ar bond cleavage of diol monoarylethers to afford 1,2-diols in good yields

Alirocumab efficiently reduces LP(A) levels by lowering Apolipoprotein (A) [APO(A)] production rate in Non-Human primates (NHP)

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