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Modelling pacemaker oscillations in lymphatic muscle cells: lengthened action potentials by two distinct system effects.
R Soc Open Sci
January 2025
School of Mathematics & Statistics, University of Sydney, Sydney, New South Wales 2006, Australia.
Lymphatic system failures contribute to cardiovascular and various other diseases. A critical function of the lymphatic vascular system is the active pumping of fluid from the interstitium back into the blood circulation by periodic contractions of lymphatic muscle cells (LMCs) in the vessel walls. As in cardiac pacemaking, these periodic contractions can be interpreted as occurring due to linked pacemaker oscillations in the LMC membrane potential (M-clock) and calcium concentration (C-clock).
View Article and Find Full Text PDFUncovering potential causal genes for undiagnosed congenital anomalies using an in-house pipeline for trio-based whole-genome sequencing.
Hum Genomics
January 2025
Division of Genome Science, Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Chungbuk, 28159, Republic of Korea.
Background: Congenital anomalies (CAs) encompass a wide spectrum of structural and functional abnormalities during fetal development, commonly presenting at birth. Identifying the cause of CA is essential for accurate diagnosis and treatment. Using a target-gene approach, genetic variants could be found in certain CA patients.
View Article and Find Full Text PDFA Novel Class of FKBP12 Ligands Rescues Premature Aging Phenotypes Associated with Myotonic Dystrophy Type 1.
Cells
November 2024
Cellular Oncology Group, Biogipuzkoa Health Research Institute, Paseo Dr. Beguiristain s/n, 20014 San Sebastian, Spain.
Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder clinically characterized by progressive muscular weakness and multisystem degeneration, which correlates with the size of CTG expansion and MBLN decrease. These changes induce a calcium and redox homeostasis imbalance in several models that recapitulate the features of premature tissue aging. In this study, we characterized the impact of a new family of FKBP12 ligands (generically named MPs or MP compounds) designed to stabilize FKBP12 binding to the ryanodine receptors and normalize calcium dysregulation under oxidative stress.
View Article and Find Full Text PDFCalcium handling abnormalities increase arrhythmia susceptibility in DMSXL myotonic dystrophy type 1 mice.
Biomed Pharmacother
November 2024
Cardiovascular Research Program, VA New York Harbor Healthcare System, New York, NY, USA; Department of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Health Sciences University, New York, NY, USA; Department of Medicine, NYU Langone School of Medicine, New York, NY, USA. Electronic address:
Background: Myotonic dystrophy type 1 (DM1) is a multiorgan disorder with significant cardiac involvement. ECG abnormalities, including arrhythmias, occur in 80 % of DM1 patients and are the second-most common cause of death after respiratory complications; however, the mechanisms underlying the arrhythmogenesis remain unclear. The objective of this study was to investigate the basis of the electrophysiological abnormalities in DM1 using the DMSXL mouse model.
View Article and Find Full Text PDFPurinergic agonists increase [Ca] in rat conjunctival goblet cells through ryanodine receptor type 3.
Am J Physiol Cell Physiol
September 2024
Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States.
ATP and benzoylbenzoyl-ATP (BzATP) increase free cytosolic Ca concentration ([Ca]) in conjunctival goblet cells (CGCs) resulting in mucin secretion. The purpose of this study was to investigate the source of the Ca mobilized by ATP and BzATP. First-passage cultured rat CGCs were incubated with Fura-2/AM, and [Ca] was measured under several conditions with ATP and BzATP stimulation.
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