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      Moderate aerobic exercise training decreases middle-aged induced pathologic cardiac hypertrophy by improving Klotho expression, MAPK signaling pathway, and oxidative stress status in Wistar rats

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          Abstract

          Objective(s):

          This study aimed to investigate the effect of aerobic training on serum levels of Klotho, cardiac tissue levels of H 2O 2 and phosphorylation of ERK1/2 and P38 as well as left ventricular internal diameter (LVID), the left ventricle wall thickness (LVWT) and fibrosis in middle-aged rats.

          Materials and Methods:

          Forty wistar rats, including young rats (n=10, 4 month-old) and middle-aged rats (n=30, 13-15 months-old) were enrolled in this experimental study. The all young and 10 middle-aged rats were sacrificed (randomly) under deep anesthesia without any exercise training as normal young control and normal middle-aged control respectively. The remaining 20 middle-aged rats participated in 4 (n=10) or 8-week (n=10) aerobic exercise training.

          Results:

          There were significant differences in the plasmatic Klotho levels and the heart tissue levels of phosphorylated-ERK1/2 (p-ERK1/2), P-P38 and H 2O 2, LVWT, LVID and fibrosis between young and middle-aged rats ( P=0.01). Plasmatic Klotho level was significantly increased after eight weeks training ( P=0.011). Also, p-ERK1/2 was significantly decreased after eight weeks and p-P38 was significantly decreased in the fourth ( P=0.01) and eight weeks of training ( P=0.01). A similar decrease was reported for aging-induced H 2O 2 in the fourth ( P=0.016) and eighth weeks ( P=0.001). LVID was significantly increased in eight weeks, but LVWT and fibrosis was significantly reduced in the eighth week ( P=0.011, P=0.028, P=0.001 respectively).

          Conclusion:

          Moderate aerobic training attenuates aging-induced pathological cardiac hypertrophy at least partially by restoring the Klotho levels, attenuating oxidative stress, and reduction in the phosphorylation of ERK1/2, P38 and fibrosis.

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          Most cited references52

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          Adult cardiac stem cells are multipotent and support myocardial regeneration.

          The notion of the adult heart as terminally differentiated organ without self-renewal potential has been undermined by the existence of a subpopulation of replicating myocytes in normal and pathological states. The origin and significance of these cells has remained obscure for lack of a proper biological context. We report the existence of Lin(-) c-kit(POS) cells with the properties of cardiac stem cells. They are self-renewing, clonogenic, and multipotent, giving rise to myocytes, smooth muscle, and endothelial cells. When injected into an ischemic heart, these cells or their clonal progeny reconstitute well-differentiated myocardium, formed by blood-carrying new vessels and myocytes with the characteristics of young cells, encompassing approximately 70% of the ventricle. Thus, the adult heart, like the brain, is mainly composed of terminally differentiated cells, but is not a terminally differentiated organ because it contains stem cells supporting its regeneration. The existence of these cells opens new opportunities for myocardial repair.
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            Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23.

            (2000)
            Proper serum phosphate concentrations are maintained by a complex and poorly understood process. Identification of genes responsible for inherited disorders involving disturbances in phosphate homeostasis may provide insight into the pathways that regulate phosphate balance. Several hereditary disorders of isolated phosphate wasting have been described, including X-linked hypophosphataemic rickets (XLH), hypophosphataemic bone disease (HBD), hereditary hypophosphataemic rickets with hypercalciuria (HHRH) and autosomal dominant hypophosphataemic rickets (ADHR). Inactivating mutations of the gene PHEX, encoding a member of the neutral endopeptidase family of proteins, are responsible for XLH (refs 6,7). ADHR (MIM 193100) is characterized by low serum phosphorus concentrations, rickets, osteomalacia, lower extremity deformities, short stature, bone pain and dental abscesses. Here we describe a positional cloning approach used to identify the ADHR gene which included the annotation of 37 genes within 4 Mb of genomic sequence. We identified missense mutations in a gene encoding a new member of the fibroblast growth factor (FGF) family, FGF23. These mutations in patients with ADHR represent the first mutations found in a human FGF gene.
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              Pathological ventricular remodeling: mechanisms: part 1 of 2.

              Despite declines in heart failure morbidity and mortality with current therapies, rehospitalization rates remain distressingly high, substantially affecting individuals, society, and the economy. As a result, the need for new therapeutic advances and novel medical devices is urgent. Disease-related left ventricular remodeling is a complex process involving cardiac myocyte growth and death, vascular rarefaction, fibrosis, inflammation, and electrophysiological remodeling. Because these events are highly interrelated, targeting a single molecule or process may not be sufficient. Here, we review molecular and cellular mechanisms governing pathological ventricular remodeling.
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                Author and article information

                Journal
                Iran J Basic Med Sci
                Iran J Basic Med Sci
                ijbms
                Iranian Journal of Basic Medical Sciences
                Mashhad University of Medical Sciences (Mashhad, Iran )
                2008-3866
                2008-3874
                September 2018
                : 21
                : 9
                : 911-919
                Affiliations
                [1 ]Department of Physical Education and Sport Science, Jolfa Branch, Islamic Azad University, Jolfa, Iran
                [2 ]Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
                [3 ]Department of Physical Education and Sport Science, University of Mohaghegh Ardabili, Ardabil, Iran
                [4 ]Department of Kinesiology, College of Agriculture, Health and Natural Resources, University of Connecticut, Connecticut, USA
                Author notes
                [* ]Corresponding author: Behrouz Baghaiee. Department of Physical Education and Sport Science, Jolfa Branch, Islamic Azad University, Jolfa, Iran. Email: behrouz_phsport@yahoo.com
                Article
                IJBMS-21-911
                6272071
                7def6e50-ee72-4b75-ab6a-8d91a8ae2c79

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 February 2018
                : 13 May 2018
                Categories
                Original Article

                exercise,fibrosis,h2o2,left ventricular hypertrophy klotho,mitogen-activated protein- kinase

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