The sodium-glucose cotransporter type 2 inhibitors reduce mortality and heart failure (HF) hospitalizations. The underlying mechanisms remain unclear but seem to be irrespective of glucose-lowering ...properties. This study aims to evaluate the impact of empagliflozin on myocardial biomechanics and correlation with markers of adverse remodeling.
Following myocardial infarct induction to create a model of HF, 14 pigs were randomly assigned in a 1:1 ratio to receive either empagliflozin 10 mg daily or placebo for 2 months. Speckle-tracking echocardiography (STE) and feature-tracking cardiac magnetic resonance (FTCMR) were performed at baseline and at the end of the study to analyze myocardial deformation. The results were correlated with markers of adverse cardiac remodeling.
Empagliflozin significantly improved STE indices. These parameters significantly correlated with adverse cardiac remodeling. In contrast, FTCMR indices showed only a trend toward improved myocardial deformation and without significant correlation with adverse cardiac remodeling. The correlation between both techniques to assess myocardial deformation was low.
Empagliflozin enhances myocardial deformation, assessed by STE techniques, in a non-diabetic porcine model of ischemic HF. This may be related to a mitigation of adverse cardiac remodeling following ischemia reperfusion injury. In contrast, FTCMR technique needs further development and validation.
Animals in the lowest BOLD tertile exhibited more adverse LV remodeling, impaired LV function, lower myocardial perfusion, and reduced energetics and capillary density (Table) Conclusions: Myocardial ...oxygenation using BOLD is a useful tool for evaluation of capillary density, and is linked to myocardial energetics, LV function and remodeling
Background: Autophagy (the cellular process responsible for the degradation and recycling of damaged proteins and organelles) is a downstream pathway which plays a role in decreasing ...ischemia-reperfusion (I-R) injury.
Cell survival, apoptosis (flow cytometry, Western Blot -WB-), and activation of the RISK pathway (the main cardiomyocyte antiapoptotic pathway; WB for pAkt, GSK-3β and PKC-straight epsilon) were ...assessed.
Summary
Lithium is widely used in the treatment of bipolar disorder, but despite its proven therapeutic efficacy, the molecular mechanisms of action are not fully understood. The present study was ...undertaken to explore lithium effects of the MEK/ERK cascade of protein kinases in astrocytes and neurons. In asynchronously proliferating rat cortical astrocytes, lithium decreased time‐ and dose‐dependently the phosphorylation of MEK and ERK, with 1 mm concentrations achieving 60 and 50% inhibition of ERK and MEK, respectively, after a 7‐day exposure. Lithium also inhibited 3Hthymidine incorporation into DNA and induced a G2/M cell cycle arrest. In serum‐deprived, quiescent astrocytes, pre‐exposure to lithium resulted in the inhibition of cell cycle re‐entry as stimulated by the mitogen endothelin‐1: under this experimental setting, lithium did not affect the rapid, peak phosphorylation of MEK taking place after 3–5 min, but was effective in inhibiting the long‐term, sustained phosphorylation of MEK. Lithium inhibition of the astrocyte MEK/ERK pathway was independent of inositol depletion. Further, compound SB216763 inhibited Tau phosphorylation at Ser396 and stabilized cytosolic β‐catenin, consistent with the inhibition of glycogen synthase kinase‐3β (GSK‐3β), but failed to reproduce lithium effects on MEK and ERK phosphorylation and cell cycle arrest. In cerebellar granule neurons, millimolar concentrations of lithium enhanced MEK and ERK phosphorylation in a concentration‐dependent manner, again through an inositol and GSK‐3β independent mechanism. These opposing effects in astrocytes and neurons make lithium treatment a promising strategy to favour neural repair and reduce reactive gliosis after traumatic injury.
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