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)


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
Issue number1-2
Publication statusPublished - Feb 2014
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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