Circadian rhythm disorder of thrombosis and thrombolysis-related gene expression in apolipoprotein E knock-out mice.
Plaque rupture and subsequent embolism as well as thrombosis are major causes of acute myocardial infarction and stroke secondary to atherosclerosis. Pai-1, t-PA, TF and ET-1 are thrombosis- and thrombolysis-related factors which play important roles in thrombosis formation and plaque rupture. Since acute myocardial infarction and stroke are more likely to occur between 6 a.m. and 12 p.m. than at another time of the day, we studied the relationship between circadian rhythm and Pai-1, t-PA, TF and ET-1 in normal and atherosclerotic mice. Atherosclerosis was developed in apoE-/- mice fed a normal diet or a high cholesterol diet. The expression of Pai-1, t-PA, TF and ET-1 in the hearts of control C57BL/6J mice and atherosclerotic mice was measured by real-time RT-PCR at different Zeitgeber times (ZT) including ZT0, ZT4, ZT8, ZT10, ZT12, ZT14, ZT16 and ZT20. The expression of Pai-1, t-PA, TF and ET-1 peaked between ZT14 and ZT16 and bottomed at ZT10 in C57BL/6J mice. Their expression in apoE-/- mice fed a normal diet lost circadian rhythm. Their expression in apoE-/- mice fed a high cholesterol diet peaked at ZT4, indicating a reverse circadian rhythm. Our result indicates that circadian changes in the expression of Pai-1, t-PA, TF and ET-1 may be involved in the onset of myocardial infarction and stroke.
Zhang
Xueqing
X
Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, PR China.
Zhao
Fengdi
F
Xu
Chen
C
Lu
Chao
C
Jin
Huiming
H
Chen
Sifeng
S
Qian
Ruizhe
R
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology; D002791:Cholesterol, Dietary; D021081:Chronobiology Disorders / Q000503:physiopathology*; D002940:Circadian Rhythm / Q000502:physiology*; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism; D013927:Thrombosis / Q000473:pathology / Q000503:physiopathology*; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism
D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D019332:Endothelin-1; D017395:Plasminogen Activator Inhibitor 1; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator