title: Premature cardiac senescence in DahlS.Z-Lepr(fa)/Lepr(fa) rats as a new animal model of metabolic syndrome.
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.
authors.forename: Keiji
authors.initials: K
authors.lastname: Takahashi
authors.forename: Miwa
authors.initials: M
authors.lastname: Takatsu
authors.forename: Takuya
authors.initials: T
authors.lastname: Hattori
authors.forename: Tamayo
authors.initials: T
authors.lastname: Murase
authors.forename: Sae
authors.initials: S
authors.lastname: Ohura
authors.forename: Yuuri
authors.initials: Y
authors.lastname: Takeshita
authors.forename: Shogo
authors.initials: S
authors.lastname: Watanabe
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Kohzo
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D016922:Cellular Senescence; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005355:Fibrosis; D005786:Gene Expression Regulation; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D051381:Rats; D020303:Rats, Inbred Dahl; D011924:Rats, Zucker; D059506:Telomere Shortening; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D018836:Inflammation Mediators