Premature cardiac senescence in DahlS.Z-Lepr(fa)/Lepr(fa) rats as a new animal model of metabolic syndrome.

Keiji Takahashi, Miwa Takatsu, Takuya Hattori, Tamayo Murase, Sae Ohura, Yuuri Takeshita, Shogo Watanabe, Toyoaki Murohara, Kohzo Nagata

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Aging is accelerated by metabolic and cardiovascular diseases, and the risk of these diseases increases with age. Obesity is an important risk factor for many age-related diseases and is linked to reduced telomere length in white blood cells. We investigated whether cardiac senescence might be enhanced in DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, which we recently established as a new animal model of metabolic syndrome. The heart of DS/obese rats was compared with that of homozygous lean littermates (DahlS.Z-Lepr+/Lepr+, or DS/lean, rats). DS/obese rats manifested hypertension as well as left ventricular hypertrophy, fibrosis, and diastolic dysfunction at 18 weeks of age. Myocardial oxidative stress and inflammation were increased in DS/obese rats compared with DS/lean rats. Telomere length in myocardial cells did not differ between the two rat strains, whereas telomerase activity and expression of the telomerase reverse transcriptase gene were increased in DS/obese rats. Expression of the senescence-associated genes for checkpoint kinase 2 (Chk2), p53, and p21 as well as that of genes related to the renin-angiotensin-aldosterone system were also up-regulated in the DS/obese rat heart. Our results indicate that DS/obese rats undergo premature cardiac senescence as well as cardiac remodeling in association with the development of diastolic dysfunction in these animals.

Original languageEnglish
Pages (from-to)35-49
Number of pages15
JournalNagoya Journal of Medical Science
Volume76
Issue number1-2
Publication statusPublished - 2014
Externally publishedYes

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Animal Models
Telomerase
Telomere
Checkpoint Kinase 2
Genes
Metabolic Diseases
Left Ventricular Hypertrophy
Renin-Angiotensin System
Oxidative Stress
Leukocytes
Fibrosis
Cardiovascular Diseases
Obesity
Hypertension
Inflammation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Takahashi, K., Takatsu, M., Hattori, T., Murase, T., Ohura, S., Takeshita, Y., ... Nagata, K. (2014). Premature cardiac senescence in DahlS.Z-Lepr(fa)/Lepr(fa) rats as a new animal model of metabolic syndrome. Nagoya Journal of Medical Science, 76(1-2), 35-49.

Premature cardiac senescence in DahlS.Z-Lepr(fa)/Lepr(fa) rats as a new animal model of metabolic syndrome. / Takahashi, Keiji; Takatsu, Miwa; Hattori, Takuya; Murase, Tamayo; Ohura, Sae; Takeshita, Yuuri; Watanabe, Shogo; Murohara, Toyoaki; Nagata, Kohzo.

In: Nagoya Journal of Medical Science, Vol. 76, No. 1-2, 2014, p. 35-49.

Research output: Contribution to journalArticle

Takahashi, K, Takatsu, M, Hattori, T, Murase, T, Ohura, S, Takeshita, Y, Watanabe, S, Murohara, T & Nagata, K 2014, 'Premature cardiac senescence in DahlS.Z-Lepr(fa)/Lepr(fa) rats as a new animal model of metabolic syndrome.', Nagoya Journal of Medical Science, vol. 76, no. 1-2, pp. 35-49.
Takahashi K, Takatsu M, Hattori T, Murase T, Ohura S, Takeshita Y et al. Premature cardiac senescence in DahlS.Z-Lepr(fa)/Lepr(fa) rats as a new animal model of metabolic syndrome. Nagoya Journal of Medical Science. 2014;76(1-2):35-49.
Takahashi, Keiji ; Takatsu, Miwa ; Hattori, Takuya ; Murase, Tamayo ; Ohura, Sae ; Takeshita, Yuuri ; Watanabe, Shogo ; Murohara, Toyoaki ; Nagata, Kohzo. / Premature cardiac senescence in DahlS.Z-Lepr(fa)/Lepr(fa) rats as a new animal model of metabolic syndrome. In: Nagoya Journal of Medical Science. 2014 ; Vol. 76, No. 1-2. pp. 35-49.
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