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Frontiers | Myofibroblast-Derived Exosome Induce Cardiac Endothelial Cell Dysfunction



1Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL, United States
2Molecular and Cellular Pathology, Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, United States
3Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, AL, United States
4Center for Translational Medicine, Temple University, Philadelphia, PA, United States
Background: Endothelial cells (ECs) play a critical role in the maintenance of vascular homeostasis and in heart function. It was shown that activated fibroblast-derived exosomes impair cardiomyocyte function in hypertrophic heart, but their effect on ECs is not yet clear. Thus, we hypothesized that activated cardiac fibroblast-derived exosomes (FB-Exo) mediate EC dysfunction, and therefore modulation of FB-exosomal contents may improve endothelial function. ....

United States , University Of Alabama At Birmingham , Van Berlo , Schaferk Angiogenic , Burnett Jc Jr , Chakrabartis Micro , Carmelietp Pl , Coll Cardiol , Arterioscler Thromb Vasc , Schultz Jel , Matrigel Corning , Sprague Dawley , Annamalaid Sreejit , Malvern Panalytical , Alix End , Keaney Jf Jr , Liul Mi , Biomed Pharmacother , University Of Alabama Birmingham , American Heart Association , Transwell Boyden Chamber , Corning Incorporated Life Sciences , National Institutes Of Health , Nunc Lab , Microplate Reader Biotek Instruments Inc , Spectra Services Inc ,

FDCA ameliorates SU5416/hypoxia-induced PASMC dysfunction


Background: Pulmonary arterial hypertension (PAH) is an incurable disease that urgently needs therapeutic approaches. Based on the therapeutic effects of fasudil and dichloroacetate (DCA) on PAH, we aimed to explore the effects and potential mechanism of a new salt, fasudil dichloroacetate (FDCA), in a SU5416 plus hypoxia (SuHx)-induced rat model of PAH.
Methods: The rat model of PAH was established by a single subcutaneous injection of SU5416 (20 mg/kg) followed by hypoxia (10% O
2) exposure for 3 weeks. FDCA (15, 45, or 135 mg/kg i.g. daily) or the positive control, bosentan (100 mg/kg i.g. daily), were administered from the first day after SU5416 injection. After 3-week hypoxia, hemodynamic parameters, and histological changes of the pulmonary arterial vessels and right ventricle (RV) were assessed. Additionally, in vitro, the effects of FDCA (50 μM), compared with equimolar doses of fasudil, DCA, or fasudil+DCA, on the proliferation, migration, and contraction of huma ....

United States , San Diego , United Kingdom , Pasmcs Sciencell , Laboratory Animals , Chemical Technology Co Ltd , Image Lab , Aipu Instrument Equipment Co Ltd , Proteintech Group , China Pharmaceutical University , Committee Of Nanjing Medical University , Bikai Laboratory Animal Company , Cell Signaling Technology , Key Laboratory Of Natural Medicine , Huaxi Electronic Technology Co Ltd , Power Lab , National Institutes , Health Guidelines , Institutional Animal Care , Use Committee , Nanjing Medical University , State Key Laboratory , Natural Medicine , Right Heart Hypertrophy , Thermo Scientific , Corning Costar ,