| First Author | Hemmeryckx B | Year | 2019 |
| Journal | Exp Gerontol | Volume | 118 |
| Pages | 1-8 | PubMed ID | 30610898 |
| Mgi Jnum | J:294423 | Mgi Id | MGI:6456347 |
| Doi | 10.1016/j.exger.2018.12.017 | Citation | Hemmeryckx B, et al. (2019) Deficiency of Bmal1 disrupts the diurnal rhythm of haemostasis. Exp Gerontol 118:1-8 |
| abstractText | BACKGROUND: Mice deficient in the circadian clock gene BMAL1 (Brain and Muscle ARNT-like protein-1) exhibit a hypercoagulable state and an enhanced arterial and venous thrombogenicity, which aggravates with age. We investigated the effect of BMAL1 deficiency in mice at a different age on the diurnal rhythm of factors involved in coagulation and fibrinolysis. MATERIALS AND METHODS: Hepatic, cardiac and brain tissues were isolated from 10- and 25-weeks-old Bmal1-deficient (BMAL1(-/-)) and wild-type (BMAL1(+/+)) mice at ZT2 and at ZT14 to analyze the mRNA expression level of genes involved in coagulation and fibrinolysis. RESULTS: Body weight and brain weight were significantly lower in all BMAL1(-/-) versus BMAL1(+/+) mice. Bmal1 deficiency disturbed the diurnal rhythm of plasminogen activator inhibitor-1 (PAI-1) in liver and plasma, but not in cardiac or brain tissues. BMAL1(+/+) livers showed diurnal fluctuations in factor (F)VII, FVII, protein S and anti-thrombin gene expression, which were not observed in BMAL1(-/-) tissues. Interestingly, tissue plasminogen activator (t-PA) expression was significantly upregulated in all BMAL1(-/-) versus BMAL1(+/+) brains at both time points. Plasma t-PA-PAI-1 complex levels were however similar for all groups. CONCLUSION: Bmal1 deficiency affected the biphasic rhythm of coagulation and fibrinolysis factors predominantly in the liver. In the brain, Bmal1-dependent control of t-PA gene expression was documented for the first time. |
