Open AccessAging induces cardiac diastolic dysfunction, oxidative stress, accumulation of advanced glycation endproducts and protein modification
Author(s) -
Li ShiYan,
Du Min,
Dolence E. Kurt,
Fang Cindy X.,
Mayer Gabriele E.,
CeylanIsik Asli F.,
LaCour Karissa H.,
Yang Xiaoping,
Wilbert Christopher J.,
Sreejayan Nair,
Ren Jun
Publication year - 2005
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9728.2005.00146.x
Subject(s) - oxidative stress , medicine , glycation , myocyte , endocrinology , oxidative phosphorylation , glutathione , diastole , protein carbonylation , biology , cardiac function curve , biochemistry , diabetes mellitus , enzyme , oxidative damage , heart failure , blood pressure
Summary Evidence suggests that aging, per se , is a major risk factor for cardiac dysfunction. Oxidative modification of cardiac proteins by non‐enzymatic glycation, i.e. advanced glycation endproducts (AGEs), has been implicated as a causal factor in the aging process. This study was designed to examine the role of aging on cardiomyocyte contractile function, cardiac protein oxidation and oxidative modification. Mechanical properties were evaluated in ventricular myocytes from young (2‐month) and aged (24–26‐month) mice using a MyoCam® system. The mechanical indices evaluated were peak shortening (PS), time‐to‐PS (TPS), time‐to‐90% relengthening (TR90) and maximal velocity of shortening/relengthening (± dL/dt). Oxidative stress and protein damage were evaluated by glutathione and glutathione disulfide (GSH/GSSG) ratio and protein carbonyl content, respectively. Activation of NAD(P)H oxidase was determined by immunoblotting. Aged myocytes displayed a larger cell cross‐sectional area, prolonged TR90, and normal PS, ± dL/dt and TPS compared with young myocytes. Aged myocytes were less tolerant of high stimulus frequency (from 0.1 to 5 Hz) compared with young myocytes. Oxidative stress and protein oxidative damage were both elevated in the aging group associated with significantly enhanced p47 phox but not gp91 phox expression. In addition, level of cardiac AGEs was ∼2.5‐fold higher in aged hearts than young ones determined by AGEs‐ELISA. A group of proteins with a molecular range between 50 and 75 kDa with pI of 4–7 was distinctively modified in aged heart using one‐ or two‐dimension SDS gel electrophoresis analysis. These data demonstrate cardiac diastolic dysfunction and reduced stress tolerance in aged cardiac myocytes, which may be associated with enhanced cardiac oxidative damage, level of AGEs and protein modification by AGEs.