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Telomere length and adrenergic-induced left ventricular dilatation and systolic chamber dysfunction in rats

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European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

Purpose

The mechanisms responsible for telomere shortening in heart failure are uncertain. We evaluated whether left ventricular (LV) dilatation and systolic chamber dysfunction produced by chronic β-adrenergic receptor (β-AR) activation is associated with leukocyte or cardiac telomere shortening.

Methods

Following 6 months of daily injections of the β-AR agonist, isoproterenol (0.02 mg/kg/day) or the saline vehicle to rats, the extent of LV dilatation and LV systolic chamber dysfunction were determined using echocardiography and isolated perfused heart procedures, and relative telomere length of leukocyte (LTL) and cardiac (CTL) deoxyribonucleic acid were determined using a quantitative real-time polymerase chain reaction assay.

Results

β-AR activation resulted in LV dilatation as indexed by increased LV diastolic diameters (9.2 ± 0.6 vs. 8.4 ± 0.9 mm, P = 0.01) and increased diastolic volume intercepts at zero pressure of the LV diastolic pressure–volume relationship (isolated, perfused heart preparation) (0.40 ± 0.06 vs. 0.37 ± 0.08 ml, P = 0.03). Moreover, β-AR activation resulted in LV systolic chamber dysfunction as indexed by reductions in LV endocardial fractional shortening (0.40 ± 0.05 vs. 0.45 ± 0.06, P = 0.01) and the slope of the LV systolic pressure–volume relation (609 ± 176 vs. 901 ± 230, P = 0.01). Although LTL decreased with age in rats receiving either the β-AR agonist or the saline vehicle (P < 0.05), neither CTL (−0.10 ± 0.14 vs. −0.15 ± 0.12, P = 0.3) nor LTL (−0.11 ± 0.19 vs. −0.15 ± 0.18, P = 0.5) were modified by β-AR activation.

Conclusion

In conclusion, chronic β-AR activation sufficient to produce LV dilatation and systolic chamber dysfunction is not associated with alterations in leukocyte or cardiac telomere length. Telomere shortening in chronic heart failure is unlikely to be attributed to chronic β-AR activation.

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Abbreviations

∆:

Percentage change

β-AR:

β-adrenergic receptor

CRP:

Plasma C-reactive protein

CTL:

Cardiac telomere length

DNA:

Deoxyribonucleic acid

EDD:

End-diastolic diameter

EDPWT:

End-diastolic posterior wall thickness

E es :

End-systolic elastance

ESD:

End-systolic diameter

ESPWT:

End-systolic posterior wall thickness

ESS:

End-systolic wall stress

FSend :

Endocardial fractional shortening

FSmid :

Midwall fractional shortening

ISO:

Isoproterenol

LTL:

Leukocyte telomere length

LV:

Left ventricular

LVEF:

Left ventricular ejection fraction

NYHA:

New York Heart Association

PCR:

Polymerase chain reaction

RWT:

Relative wall thickness

S:

Single copy gene repeat copy number

SD:

Standard deviation

T:

Telomere repeat copy number

V 0 :

Volume intercept at zero pressure

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Acknowledgments

This work was supported by the National Research Foundation and the University Research Council of the University of the Witwatersrand.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, Johannesburg, 2193, South Africa

    Andrew R. Raymond, Bryan Hodson, Angela J. Woodiwiss, Gavin R. Norton & Richard L. Brooksbank

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  1. Andrew R. Raymond
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  2. Bryan Hodson
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  3. Angela J. Woodiwiss
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  4. Gavin R. Norton
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  5. Richard L. Brooksbank
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Correspondence to Richard L. Brooksbank.

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Communicated by Keith Phillip George.

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Raymond, A.R., Hodson, B., Woodiwiss, A.J. et al. Telomere length and adrenergic-induced left ventricular dilatation and systolic chamber dysfunction in rats. Eur J Appl Physiol 113, 2803–2811 (2013). https://doi.org/10.1007/s00421-013-2722-8

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  • DOI: https://doi.org/10.1007/s00421-013-2722-8

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