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

Behrouz Baghaiee; Pouran Karimi; Marefat Siahkouhian; Linda S Pescatello

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

Iran J Basic Med Sci. 2018 Sep;21(9):911-919.

Authors

Behrouz Baghaiee¹, Pouran Karimi², Marefat Siahkouhian³, Linda S Pescatello⁴

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.

PMID: 30524691
PMCID: PMC6272071

Abstract

Objectives: This study aimed to investigate the effect of aerobic training on serum levels of Klotho, cardiac tissue levels of H₂O₂ 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 H₂O₂, 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 H₂O₂ 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.

Keywords: Exercise; Fibrosis; H2O2; Left ventricular hypertrophy Klotho; Mitogen-activated protein- kinase.