Atrial inflammation is critical to atrial fibrillation initiation and progression. Although left atrial dilatation is a risk factor for atrial fibrillation, the mechanism linking atrial dilatation and inflammation is unclear. We evaluated the mechanisms underlying infiltration of macrophages induced by stretch of atrial myocytes. Murine macrophages were co-cultured with HL-1 murine atrial myocyte-derived cells. Mechanical stretch applied to atrial myocytes induced transwell macrophage migration. The gap junction-channel blocker carbenoxolone and the non-specific ATP-signaling modifiers apyrase and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate inhibited the enhanced migration. Mechanical stretch of atrial myocytes induced transient increase in extracellular ATP concentration, which was inhibited by carbenoxolone. siRNA knockdown of pannexin-2 inhibited ATP release and macrophage migration. Mice underwent transverse aortic constriction or sham procedure. Transverse aortic constriction procedure induced macrophage infiltration. Daily carbenoxolone administration significantly inhibited macrophage infiltration in the atrium. Thus, mechanical stretch of atrial myocytes induces macrophage migration by ATP released through gap-junction channels, at least in part, in vitro. Administering a gap junction family-channel blocker inhibited this inflammatory change in vivo.
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http://dx.doi.org/10.1254/jphs.12202fp | DOI Listing |
Nat Commun
January 2025
Interfakultäres Institut für Biochemie, University of Tübingen, Tübingen, Germany.
A balanced activity of cGMP signaling contributes to the maintenance of cardiovascular homeostasis. Vascular smooth muscle cells (VSMCs) can generate cGMP via three ligand-activated guanylyl cyclases, the NO-sensitive guanylyl cyclase, the atrial natriuretic peptide (ANP)-activated GC-A, and the C-type natriuretic peptide (CNP)-stimulated GC-B. Here, we study natriuretic peptide signaling in murine VSMCs and atherosclerotic lesions.
View Article and Find Full Text PDFPhysiol Res
December 2024
Children's Heart Center, Second Faculty of Medicine, Charles University and Motol University Hospital, Praha, Czech Republic.
Although the heart atria have a lesser functional importance than the ventricles, atria play an important role in the pathophysiology of heart failure and supraventricular arrhythmias, particularly atrial fibrillation. In addition, knowledge of atrial morphology recently became more relevant as cardiac electrophysiology and interventional procedures in the atria gained an increasingly significant role in the clinical management of patients with heart disease. The atrial chambers are thin-walled, and several vessels enter at the level of the atria.
View Article and Find Full Text PDFCells
January 2025
Institute of Anatomy & Cell Biology, Faculty of Medicine, Justus-Liebig-University, Aulweg 123, 35392 Giessen, Germany.
Vascular smooth muscle cell (SMC) relaxation by guanylyl cyclases (GCs) and cGMP is mediated by NO and its receptor soluble GC (sGC) or natriuretic peptides (NPs) ANP/BNP and CNP with the receptors GC-A and GC-B, respectively. It is commonly accepted that cultured SMCs differ from those in intact vessels. Nevertheless, cell culture often remains the first step for signaling investigations and drug testing.
View Article and Find Full Text PDFOrphanet J Rare Dis
January 2025
Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan.
Background: Transient receptor potential cation channel subfamily V member 2 (TRPV2) functions as a stretch-sensitive calcium channel, with overexpression in the sarcolemma of skeletal and cardiac myocytes leading to detrimental calcium influx and triggering muscle degeneration. In our previous pilot study, we showed that tranilast, a TRPV2 inhibitor, reduced brain natriuretic peptide levels in two patients with muscular dystrophy and advanced heart failure. Building on this, we performed a single-arm, open-label, multicenter study herein to evaluate the safety and efficacy of tranilast in the treatment of advanced heart failure in patients with muscular dystrophy.
View Article and Find Full Text PDFLife Sci
February 2025
Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xincheng District, Xi'an, Shaanxi 710004, China. Electronic address:
Aims: Glucosamine, a widely used dietary supplement, has been linked to potential cardiovascular risks, including atrial fibrillation (AF). This study aimed to investigate the effects of long-term glucosamine supplementation on AF susceptibility and the underlying mechanisms.
Materials And Methods: C57BL/6 J mice were treated with low-dose (15 mg/kg/day) or high-dose (250 mg/kg/day) glucosamine via drinking water for 6 weeks.
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