Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
Exp Gerontol. 2011 Dec;46(12):994-9. doi: 10.1016/j.exger.2011.09.003. Epub 2011 Sep 21.
To evaluate the effects of aging on the circadian gene expression of coagulation and fibrinolytic factors in the mouse tissues, we examined temporal mRNA expression profiles of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), tissue factor (TF), and thrombomodulin (TM) genes together with circadian clock genes in the brains, hearts and livers of young (5weeks old) and aged (15months old) mice. Cardiac mRNA expression of β-myosin heavy chain (β-MHC), a molecular marker of cardiac hypertrophy, was obviously increased in the aged mice. Rhythmic expression of the clock genes mPer2 and BMAL1 in these organs was almost identical between young and aged mice, whereas that of PAI-1, TF and TM mRNAs and of clock-controlled genes such as DBP and Dec1 were damped to low levels in the livers of aged mice. Expression levels of tPA mRNA were significantly decreased and those of TF were significantly elevated throughout the day in the brain of aged mice. Expression levels of PAI-1 in the heart of aged mice were continuously elevated over 2-fold the peak levels of young mice throughout the day. However, day/night fluctuations in plasma PAI-1 levels were unaffected by aging. Aging tissue- and time-dependently affects the mRNA expression of coagulation and fibrinolytic factors. Aging-dependent constitutive PAI-1 induction in the heart might be a risk factor for cardiovascular diseases that is independent of plasma PAI-1 levels.
为了评估衰老对小鼠组织中凝血和纤维蛋白溶解因子的昼夜基因表达的影响，我们检测了纤溶酶原激活物抑制剂-1（PAI-1）、组织型纤溶酶原激活物（tPA）、组织因子（TF）和血栓调节蛋白（TM）基因与昼夜节律基因在年轻（5 周龄）和衰老（15 月龄）小鼠的大脑、心脏和肝脏中的时间mRNA 表达谱。衰老小鼠心脏中β-肌球蛋白重链（β-MHC）的mRNA 表达明显增加，这是心脏肥大的分子标志物。这些器官中时钟基因 mPer2 和 BMAL1 的节律性表达在年轻和衰老小鼠之间几乎相同，而 PAI-1、TF 和 TM 的 mRNA 以及时钟控制基因如 DBP 和 Dec1 的表达在衰老小鼠的肝脏中被抑制到低水平。tPA mRNA 的表达水平在衰老小鼠的大脑中全天显著降低，而 TF 的表达水平全天显著升高。衰老小鼠心脏中 PAI-1 的表达水平全天持续升高，是年轻小鼠峰值水平的两倍多。然而，衰老对血浆 PAI-1 水平的昼夜波动没有影响。衰老组织和时间依赖性地影响凝血和纤维蛋白溶解因子的 mRNA 表达。衰老依赖性的心脏中 PAI-1 的组成性诱导可能是一种独立于血浆 PAI-1 水平的心血管疾病的危险因素。
