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Impaired Activity of Ryanodine Receptors Contributes to Calcium Mishandling in Cardiomyocytes of Metabolic Syndrome Rats
Conclusion Principal findings of this work are that abnormal Ca2+ transient amplitude, contractile dysfunction; and impaired relaxation of MetS cardiomyocytes underlies intrinsic dysfunctional RyR2 and SERCA pump. Abnormal activity of RyRs was evidenced by its decreased ability to bind [3H]-ryanodine. Although the MetS condition does not modify RyR2 protein expression, its phosphorylation at Ser2814 is decreased, which impairs its capacity for activation during ECC. The dysfunctional RyRs, together with a decreased activity of SERCA pump due to decreased Thr17-PLN phosphorylation suggest a downregulation of CaMKII in MetS...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

Atrial Transcriptional Profiles of Molecular Targets Mediating Electrophysiological Function in Aging and Pgc-1 β Deficient Murine Hearts
Conclusion: These findings limit the possible roles of gene transcriptional changes in previously reported age-dependent pro-arrhythmic electrophysiologial changes observed in Pgc-1β-/- atria to an altered Ca2+-ATPase (Atp2a2) expression. This directly parallels previously reported arrhythmic mechanism associated with p21-activated kinase type 1 deficiency. This could add to contributions from the direct physiological outcomes of mitochondrial dysfunction, whether through reactive oxygen species (ROS) production or altered Ca2+ homeostasis. Introduction Atrial arrhythmias constitute a major public health pro...
Source: Frontiers in Physiology - April 23, 2019 Category: Physiology Source Type: research

Apelin-13 Suppresses Neuroinflammation Against Cognitive Deficit in a Streptozotocin-Induced Rat Model of Alzheimer ’s Disease Through Activation of BDNF-TrkB Signaling Pathway
Conclusion The data in this manuscript demonstrates that apelin-13 upregulates BDNF against STZ-induced congnitive impairment by suppressing glial cell activity and inflammatory factors release. This suggests apelin signaling may be a new target in the treatment of AD. Ethics Statement All experimental protocols were carried out according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals approved by the Central South University at XiangYa Animal Care and Use Committee. Author Contributions XqQ and LH conceived the study and contributed to its experimental design. HqL carried out the...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

Canagliflozin Inhibits Human Endothelial Cell Proliferation and Tube Formation
In conclusion, the present study identified canagliflozin as a potent inhibitor of human EC proliferation. The anti-proliferative action of canagliflozin is observed in ECs isolated from both the venous and arterial circulation, and is partly due to the blockade of cyclin A expression. In addition, this study found that canagliflozin inhibits tube formation in cultured ECs and mouse aortic rings. Notably, these actions are specific for canagliflozin and not seen with other SGLT2 inhibitors. The ability of canagliflozin to exert these pleiotropic effects on EC function may contribute to both the adverse and salutary actions...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research