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An NRF2/β3-Adrenoreceptor Axis Drives a Sustained Antioxidant and Metabolic Rewiring Through the Pentose-Phosphate Pathway to Alleviate Cardiac Stress.
Circulation
March 2025
Institute of Experimental and Clinical Research (IREC), Pharmacology and Therapeutics (FATH), Cliniques Universitaires St. Luc and Université catholique de Louvain, Brussels, Belgium (L.Y.M.M., H.E., D.d.M., R.V., N.F., J.-L.B.).
Background: Cardiac β3-adrenergic receptors (ARs) are upregulated in diseased hearts and mediate antithetic effects to those of β1AR and β2AR. β3AR agonists were recently shown to protect against myocardial remodeling in preclinical studies and to improve systolic function in patients with severe heart failure. However, the underlying mechanisms remain elusive.
View Article and Find Full Text PDFCholesterol inhibits assembly and oncogenic activation of the EphA2 receptor.
Commun Biol
March 2025
Department of Biochemistry & Cellular and Molecular Biology, University of Tennessee, Knoxville, TN, USA.
The receptor tyrosine kinase EphA2 drives cancer malignancy by facilitating metastasis. EphA2 can be found in different self-assembly states: as a monomer, dimer, and oligomer. However, we have a poor understanding regarding which EphA2 state is responsible for driving pro-metastatic signaling.
View Article and Find Full Text PDFP21-Activated Kinase 2 as a Novel Target for Ventricular Tachyarrhythmias Associated with Cardiac Adrenergic Stress and Hypertrophy.
Adv Sci (Weinh)
March 2025
Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, 646000, China.
Ventricular arrhythmias associated with cardiac adrenergic stress and hypertrophy pose a significant clinical challenge. We explored ventricular anti-arrhythmic effects of P21-activated kinase 2 (Pak2), comparing in vivo and ex vivo cardiomyocyte-specific Pak2 knockout (Pak2) or overexpression (Pak2) murine models, under conditions of acute adrenergic stress, and hypertrophy following chronic transverse aortic constriction (TAC). Pak2 was downregulated 5 weeks following the latter TAC challenge.
View Article and Find Full Text PDFEnhancement of mitochondrial calcium uptake is cardioprotective against maladaptive hypertrophy by retrograde signaling uptuning Akt.
Proc Natl Acad Sci U S A
March 2025
Department of Biomedical Sciences, University of Padova, Padova 35131, Italy.
Regulation of mitochondrial Ca uptake is critical in cardiac adaptation to chronic stressors. Abnormalities in Ca handling, including mitochondrial uptake mechanisms, have been implicated in pathological heart hypertrophy. Enhancing mitochondrial Ca uniporter (MCU) expression has been suggested to interfere with maladaptive development of heart failure.
View Article and Find Full Text PDFDexmedetomidine administration is associated with reduced mortality in patients with sepsis-induced acute respiratory distress syndrome: a retrospective study.
BMC Anesthesiol
March 2025
Department of Emergency Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, Jiangsu, China.
Background: Although studies have revealed the benefits of using dexmedetomidine (DEX) in treating rodent models of acute lung injury (ALI) by improving their survival rates, clinical investigation on the effect of DEX on patients with acute respiratory distress syndrome (ARDS) remains scarce. Through this retrospective study, we aim to better understand the underlying mechanism of sepsis-induced ARDS and the effect of DEX on patients' standard treatment.
Methods: A total of 208 patients with sepsis-induced ARDS, admitted to the intensive care unit (ICU) at Affiliated Hospital of Jiangsu University, China, from January 2017 to December 2019, were included.
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