In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. suppl_16 ( 2007-10-16)
Abstract:
The ventricular peripheral conduction system (PCS) is composed of unique cardiomyocytes responsible in health for the coordinated contraction of every working cardiomyoctye. Although isolated PCS cells have been studied extensively, in vivo study has been limited by difficulties in identifying large numbers of PCS cells, making it unclear how the PCS responds to disease stimuli. Methods: To address the hypothesis of whether the PCS undergoes hypertrophy with pressure-overload, we employed a novel EGFP-Connexin40 knock-in transgenic mouse which specifically labels Cx40-expressing cells with enhanced green fluorescent protein (EGFP). The Cx40EGFP heterozygote mouse allows the visualization of the entire PCS at the macro and cellular level and, in previous work, has been shown to have a normal phenotype. We then surgically induced left ventricular hypertrophy (LVH) using transaortic constriction (TAC). Functional echocardiography confirmed LVH averaging a 94 % increase in LV/body weight after 4 weeks with preserved systolic function. Sacrifice confirmed an average 79% increased heart weight (similar to control TAC). Results: EGFP positive conduction cells measured in whole heart sections were smaller at baseline by 46% (p 〈 .001) in cross sectional area compared with working cardiomyocytes confirming published data on smaller conduction cell size. Most interestingly, EGFP positive PCS cells also underwent hypertrophy increasing by 30% (p 〈 .001) in response to load. Working cardiomyocytes increased in cell size by 42% (p 〈 .001) after TAC. Immunohistochemistry (IH) was used to confirm the identity of EGFP cells as conduction tissue. Additionally, IH showed a marked increase in expression of the cardiac transcription factor Nkx2–5 in PCS cells relative to working cells. Conclusions: We have shown for the first time that peripheral conduction system cardiomyocytes undergo hypertrophy with pressure-overload in a mouse model. In conjunction with our previous finding that Nkx2–5 increases with pressure-overload, this provides an initial characterization of PCS pathophysiology from a cellular perspective.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/circ.116.suppl_16.II_288-c
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2007
detail.hit.zdb_id:
1466401-X
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