Risultati per: Nota 13 AIFA - Guida pratica

Circulation, Volume 148, Issue Suppl_1, Page A14250-A14250, November 6, 2023. Objectives:DJ-1 protein is a multifunctional protein with cardioprotective effects against acute myocardial ischemia-reperfusion injury (IRI). This study aims to elucidate whether ND-13, a small peptide derived from DJ-1, can confer acute cardioprotection after IRI by preserving mitochondrial homeostasis through improvements in mitochondrial respiratory capacity and regulating the balance between mitochondrial fusion/fission. By enhancing mitochondrial respiration and maintaining the integrity of the mitochondrial network, ND-13 may provide a novel therapeutic strategy for cardioprotection in cardiomyocytes following IRI.Methods:In vitro,ex vivoandin vivomurine models of IRI were used to elucidate the cardioprotective effects of ND-13. Infarct size, cardiac function and mitochondrial function were assessed.Results:ND-13 was shown to confer cardioprotection in three distinct models of IRI: (i)in vitro, cardiomyocyte (CM) death was reduced by 42% (64±1% untreated vs 37±2% treated; p≤0.01); (ii)ex vivoLangendorrf, with 43% decrease in infarct size (51±6.4% untreated vs 29±8.8% treated; p≤0.05); (iii)in vivo, with 35% reduction in infarct size (49±6.4% untreated vs 32±5.0% treated; p≤0.0001). CMs treated with ND-13 in thein vitromodel of IRI demonstrated a significant increase in mitochondrial respiration rates, (basal: untreated 37±3 vs treated 63±10 pmol/min/cells, p≤0.05; maximal: untreated 286±20 vs treated 494±53 pmol/min/cells, p≤0.001; and spare respiratory capacity: untreated 251±18 vs treated 421±43 pmol/min/cells, p≤0.001) and a significant increase in levels of cytosolic ATP (untreated 4.0 ± 0.3 vs treated 5.6 ± 0.5 μM, p≤0.05).Conclusion:We demonstrate for the first time, cardioprotection with the DJ-1-derived peptide, ND-13, and this beneficial effect appears to be mediated by its mitoprotective actions with enhanced mitochondrial respiratory efficiency and increased ATP production. Upcoming research aims to explore if ND-13 promotes oxidative phosphorylation by directly binding to complexes of the electron transport chain to maximize respiratory function or by enhancing pyruvate dehydrogenase activity, thereby potentially influencing the regulation of the fission/fusion process.

Circulation, Volume 148, Issue Suppl_1, Page A16549-A16549, November 6, 2023. Introduction:Randomized controlled trials in the young population concluded that moderate-to-vigorous physical activity (MVPA) was ineffective in lowering blood pressure (BP). The associations of cumulative sedentary time (ST), light physical activity (LPA), and MVPA with BP from ages 11 – 24 years, the isotemporal substitution of ST with LPA or MVPA, and the mediation path through which movement behaviour exact their impact on BP was examined.Hypothesis:Increased ST would be associated with increased BP while cumulative LPA and MVPA would be associated with decreased BP.Methods:Altogether 2513 children (61% female) from the Avon Longitudinal Study of Parents and Children birth cohort, UK who had data on at least one time-point measure of accelerometer-based movement behaviour across the follow-up and complete BP measures at ages 11, 15, and 24 years clinic visits were studied. MVPA was categorized into ≥60mins/day or less according to WHO’s PA guidelines. Longitudinal associations and isotemporal substitutions were examined with generalized linear-mixed effect models whereas the mediation path was examined using structural equation models, adjusting for cardiometabolic and other lifestyle factors.Results:After full adjustment, a 1-minute cumulative ST from ages 11-24 years was positively associated with increased systolic BP (0.009 mmHg [95% CI 0.007 – 0.011]; p

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