| Remodeling of the Peripheral Cardiac Conduction System in Response to Pressure-Overload. | |
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MedLine Citation:
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PMID: 22307665 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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How chronic pressure-overload affects the Purkinje fibers of the ventricular peripheral conduction system (PCS) is not known. Here, we employ a Connexin40 knock-out/Enhanced Green Fluorescent Protein knock-in transgenic mouse model to specifically label the PCS. We hypothesized that the subendocardially-located PCS would remodel following chronic pressure-overload and therefore analyzed cell size, markers of hypertrophy as well as PCS specific connexin and ion channel expression patterns. Left ventricular hypertrophy with preserved systolic function was induced by 30 days of surgical trans-aortic constriction (TAC). After TAC, we observed that PCS cardiomyocytes hypertrophied by 23% (p<0.05) and that micro-dissected PCS tissue exhibited upregulated markers of hypertrophy. PCS cardiomyocytes showed a 98% increase in the number of Connexin40 positive gap junction particles with an associated two-fold increase in gene expression (p<0.05). We also identified a 50% reduction in Connexin43 gap junction particles located at the interface between PCS cardiomyocytes and the working cardiomyocyte. In addition, we measured a four-fold increase of the ion channel, HCN4, 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 proof-of-concept that pressure-overload induces specific cellular changes, not just within the working myocardium but also within the specialized PCS. |
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Authors:
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Brett S Harris; Catalin F Baicu; Nicole Haghshenas; Harinath Kasiganesan; Dimitri Scholz; Mary S Rackley; Lucile Miquerol; Daniel Gros; Rupak Mukherjee; Terrence X O'Brien |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-3 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: - ISSN: 1522-1539 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Medical University of South Carolina. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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