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The senescence‐accelerated mouse: a model for the investigation of age‐related oxidative stress and diastolic dysfunction
Author(s) -
Reed Alana Leigh,
Fan TaiHwang Michael,
Dudley Samuel C,
Sutliff Roy L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.970.39
Subject(s) - oxidative stress , senescence , diastole , medicine , endocrinology , cardiology , blood pressure
Diastolic dysfunction (DD) is characterized by impaired active relaxation, increased stiffness, and often progresses to diastolic heart failure. Although DD has been associated with aging and oxidative stress in humans, mechanisms of DD have proven difficult to study due to lack of relevant animal models. We have used the senescence‐accelerated mouse model (SAM) to investigate DD. This model mimics many geriatric disorders observed in humans and consists of two strains, senescence‐prone (SAMP8) and senescence‐resistant controls (SAMR1). Oxidative stress was measured in aortas using electron spin resonance. Pulsed‐wave Doppler echocardiography was used to assess blood flow velocity (E/A), tissue‐Doppler imaging was used to assess mitral annulus velocity (E’/A’), and color M‐mode imaging was used to measure the propagation inflow velocity (V p ). SAMP8 mice had a two‐fold increase in vascular superoxide compared to controls (p<0.05; n=3). The E/A ratio was reduced from 4.2 ± 0.1 cm/s in SAMR1 to 1.9 ± 0.3 cm/s in SAMP8 mice. The E’/A’ ratio was similarly reduced from 1.6 ± 0.1 to 0.6 ± 0.1 in SAMR1 vs. SAMP8 mice, respectively. Finally, V p was decreased from 42.7 ± 2.4 cm/s in SAMR1 to 24.7 ± 2.0 cm/s in SAMP8 mice (p<0.05; n=3). These data suggest that aging is associated with DD and oxidative stress in this model; therefore, it may be useful in elucidating the mechanisms behind DD.