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 journalArticlepeer-review

10 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 - Feb 2014
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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