title: RAGE upregulation and nuclear factor-kappaB activation associated with ageing rat cardiomyocyte dysfunction.
abstract: Evidence suggests that ageing is a major risk factor for cardiac dysfunction. Interactions between advanced glycation endproducts (AGEs) and the receptor for AGEs (RAGE) are known to cause chronic cellular activation, including activation of nuclear factor-kappaB (NF-kappaB), which has been implicated as a causal factor in the ageing process. To assess whether cardiomyocyte contractile function and the interaction of AGEs with RAGE in the heart are altered in ageing, 25- and 2-month-old male rats were compared. Mechanical properties were assessed in ventricular myocytes using an edge-detection system, including peak twitch amplitude (PTA), time-to-PTA (TPS), time-to-75% relengthening (TR75) and maximal velocity of shortening/relengthening (+/-dL/dt) in ventricular myocytes. AGEs were detected by using a fluorescence assay. The expression of RAGE and NF-kappaB was assessed through a Western blot analysis. Compared with young myocytes, aged myocytes displayed a prolonged TR75 at 1 Hz. With increasing stimulus frequency (from 2 to 4 Hz), aged myocytes' PTA was significantly reduced relative to young myocytes. Aged rat hearts displayed high level of AGEs, RAGE upregulation and NF-kappaB activation. These findings demonstrate impaired cardiomyocyte relaxation and reduced tolerance to increased stimulus frequency in aged rats, which might be associated with enhanced AGEs, RAGE expression, and NF-kappaB activation.
authors.affiliation: Department of Toxicology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Gao
authors.forename: C
authors.initials: C
authors.lastname: Yang
authors.forename: Y Y
authors.initials: YY
authors.lastname: Wang
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: H L
authors.initials: HL
authors.lastname: Chen
authors.forename: X D
authors.initials: XD
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Liu
authors.forename: W L
authors.initials: WL
authors.lastname: Li
authors.forename: X J
authors.initials: XJ
authors.lastname: Qin
authors.forename: X
authors.initials: X
authors.lastname: Liang
authors.forename: C X
authors.initials: CX
authors.lastname: Hai
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D016922:Cellular Senescence / Q000502:physiology*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic