Remodeling of the peripheral cardiac conduction system in response to pressure overload
| Autor: | Harinath Kasiganesan, Brett S. Harris, Lucile Miquerol, Daniel Gros, Mary S. Rackley, Terrence X. O'Brien, Dimitri Scholz, Rupak Mukherjee, Nicole Haghshenas, Catalin F. Baicu |
|---|---|
| Přispěvatelé: | Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Physiology
MESH: Constriction Action Potentials Fluorescent Antibody Technique Connexin MESH: Myocytes Cardiac Cell Count 030204 cardiovascular system & hematology Left ventricular hypertrophy Connexins Muscle hypertrophy MESH: Cyclic Nucleotide-Gated Cation Channels MESH: Heart Conduction System Electrocardiography Mice Integrative Cardiovascular Physiology and Pathophysiology 0302 clinical medicine Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Image Processing Computer-Assisted MESH: Microscopy Confocal Myocytes Cardiac MESH: Animals MESH: Fluorescent Antibody Technique MESH: Action Potentials MESH: Cell Size 0303 health sciences Microscopy Confocal Ventricular Remodeling MESH: Real-Time Polymerase Chain Reaction Gap junction MESH: Purkinje Fibers Constriction MESH: Image Processing Computer-Assisted humanities ErbB Receptors medicine.anatomical_structure Echocardiography Cardiology Female Electrical conduction system of the heart Cardiology and Cardiovascular Medicine MESH: Pressure medicine.medical_specialty MESH: Hemodynamics Purkinje fibers MESH: Mice Transgenic Blotting Western Cyclic Nucleotide-Gated Cation Channels Cardiomegaly Mice Transgenic MESH: Ventricular Remodeling MESH: Receptor Epidermal Growth Factor [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Real-Time Polymerase Chain Reaction Purkinje Fibers 03 medical and health sciences Heart Conduction System Physiology (medical) Internal medicine Pressure medicine Animals MESH: Blotting Western Ventricular remodeling MESH: Mice Cell Size 030304 developmental biology Pressure overload MESH: Cell Count Hemodynamics medicine.disease MESH: Electrocardiography MESH: Connexins MESH: Echocardiography MESH: Cardiomegaly MESH: Female |
| Zdroj: | AJP-Heart and Circulatory Physiology AJP-Heart and Circulatory Physiology, American Physiological Society, 2012, 302 (8), pp.H1712-25. ⟨10.1152/ajpheart.00621.2011⟩ AJP-Heart and Circulatory Physiology, 2012, 302 (8), pp.H1712-25. ⟨10.1152/ajpheart.00621.2011⟩ |
| ISSN: | 0363-6135 1522-1539 |
| DOI: | 10.1152/ajpheart.00621.2011⟩ |
| Popis: | How chronic pressure overload affects the Purkinje fibers of the ventricular peripheral conduction system (PCS) is not known. Here, we used a connexin (Cx)40 knockout/enhanced green fluorescent protein knockin transgenic mouse model to specifically label the PCS. We hypothesized that the subendocardially located PCS would remodel after chronic pressure overload and therefore analyzed cell size, markers of hypertrophy, and PCS-specific Cx and ion channel expression patterns. Left ventricular hypertrophy with preserved systolic function was induced by 30 days of surgical transaortic constriction. After transaortic constriction, we observed that PCS cardiomyocytes hypertrophied by 23% ( P < 0.05) and that microdissected PCS tissue exhibited upregulated markers of hypertrophy. PCS cardiomyocytes showed a 98% increase in the number of Cx40-positive gap junction particles, with an associated twofold increase in gene expression ( P < 0.05). We also identified a 50% reduction in Cx43 gap junction particles located at the interface between PCS cardiomyocytes and the working cardiomyocyte. In addition, we measured a fourfold increase of an ion channel, hyperpolarization-activated cyclic nucleotide-gated channel (HCN)4, throughout the PCS ( P < 0.05). As a direct consequence of PCS remodeling, we found that pressure-overloaded hearts exhibited marked changes in ventricular activation patterns during normal sinus rhythm. These novel findings characterize PCS cardiomyocyte remodeling after chronic pressure overload. We identified significant hypertrophic growth accompanied by modified expression of Cx40, Cx43, and HCN4 within PCS cardiomyocytes. We found that a functional outcome of these changes is a failure of the PCS to activate the ventricular myocardium normally. Our findings provide a proof of concept that pressure overload induces specific cellular changes, not just within the working myocardium but also within the specialized PCS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|