Clock Genes Display Rhythmic Expression in Human Hearts
Clock Genes Display Rhythmic Expression in Human Hearts
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DOI：
10.1080/07420520902924939
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发表时间：
2009-01-01
影响因子：
2.8
通讯作者：
Ekmekcioglu, Cem
中科院分区：
文献类型：
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作者：
Leibetseder, Valentin;Humpeler, Susanne;Ekmekcioglu, Cem
到目前为止，心脏中的时钟基因只在啮齿动物中被描述过，这些基因的改变与各种心肌功能障碍有关。在这项研究中，我们分析了时钟基因在人类心脏中的表达。原位心脏移植获得冠心病患者16例，心肌病患者39例，健康供体9例（男52例，女12例，平均年龄55.711.2岁，16 ~ 70岁）左乳头肌。我们利用实时PCR技术检测了PER1、PER2、BMAL1和CRY1的mRNA水平，并利用滑动均值和余弦函数分析了它们的节律性表达。此外，我们寻求三组之间的差异（通过方差分析）在总24小时期间和单独的时间箱。所有四个时钟基因都在人类心脏中表达。PER mrna的峰期（昼夜节律高峰时间）发生在早晨(PER1: 07:44h[峰值水平比低谷高187%，p = 0.008]； PER2: 09:42h[峰值水平比低谷高254%，p = 0.008]。[0001]，晚上21:44h BMAL1 mRNA[峰值比低谷高438%；p。]。三组之间的节奏模式没有发现差异。各组CRY1 mRNA均未检测到昼夜节律。PER1、PER2和BMAL1 mrna在人类心脏中揭示了明确的昼夜节律，其分期与啮齿动物的分期相反。心脏组织中mRNA时钟基因水平的昼夜节律振幅比迄今为止研究的任何其他人体组织都更明显。心肌PER mrna的峰期和心肌BMAL1的低谷期与一天中心肌事件最频繁的时间一致。
Thus far, clock genes in the heart have been described only in rodents, and alterations of these genes have been associated with various myocardial malfunctions. In this study, we analyzed the expression of clock genes in human hearts. Left papillary muscles of 16 patients with coronary heart disease, 39 subjects with cardiomyopathy, and 9 healthy donors (52 males and 12 females, mean age 55.711.2; 16-70 yrs) were obtained during orthotopic heart transplantation. We assessed the mRNA levels of PER1, PER2, BMAL1, and CRY1 by real time PCR and analyzed their rhythmic expression by sliding means and Cosinor functions. Furthermore, we sought for differences between the three groups (by ANOVAs) for both the total 24h period and separate time bins. All four clock genes were expressed in human hearts. The acrophases (circadian rhythm peak time) of the PER mRNAs occurred in the morning (PER1: 07:44h [peak level 187% higher than trough, p = .008]; PER2: 09:42h [peak 254% higher than trough, p .0001], and BMAL1 mRNA in the evening at 21:44h [peak 438% higher than trough; p .0001]. No differences were found in the rhythmic patterns between the three groups. No circadian rhythm was detected in CRY1 mRNA in any group. PER1, PER2, and BMAL1 mRNAs revealed clear circadian rhythms in the human heart, with their staging being in antiphase to those in rodents. The circadian amplitudes of the mRNA clock gene levels in heart tissue are more distinct than in any other human tissue so far investigated. The acrophase of the myocardial PER mRNAs and the trough of the myocardial BMAL1 coincide to the time of day of most frequent myocardial incidents.