Thesis or Dissertation Cardiac hypertrophy is exacerbated in aged mice lacking the osteoprotegerin gene

Hao, Yilin  ,  Tsuruda, Toshihiro  ,  Sekita-Hatakeyama, Yoko  ,  Kurogi, Syuji  ,  Kubo, Keishi  ,  Sakamoto, Sumiharu  ,  Nakamura, Midori  ,  Udagawa, Nobuyuki  ,  Sekimoto, Tomohisa  ,  Hatakeyama, Kinta  ,  Chosa, Etsuo  ,  Asada, Yujiro  ,  Kitamura, Kazuo

2016-05 , European Society of Cardiology
We conducted experiments using 2.5- and 12-month-old OPG2/2 mice and age-matched wild-type (WT) mice and compared the morphology and function of the left ventricle (LV). Both 2.5- and 12-month-old OPG2/2 mice showed a higher systolic blood pressure and a greater heart weight/body weight ratio than age-matched WT mice. Twelvemonth-old OPG2/2 mice had a significantly larger LV chamber and reduced wall thickness compared with age-matchedWT mice, and contractile function was decreased. The morphological differences were accompanied by an increase in the number of apoptotic cells and activation of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in the LV of 12-month-old OPG2/2 mice. Correspondingly, OPG small interfering RNA induced the expressions of TRAIL and cleaved caspase-3 in cultured cardiac myocytes. In addition, these mice revealed a decrease in interstitial fibrosis, activation of matrix metalloproteinase (MMP)-2 and tissue inhibitors of MMP-1 and -2, and inactivation of procollagen a1 synthesis. Moreover, intraperitoneal administration of recombinant OPG to either 2.5- or 12- month-old OPG2/2 mice for 28 days led to partial improvement of LV structure and function without affecting systolic blood pressure.

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