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腾讯登录Cell Rep：昼夜节律的破坏会影响体内血管的生长
| 导读 | 昼夜节律的破坏会影响体内血管的生长，从而导致如糖尿病、肥胖和癌症等的发生，据瑞典林雪平大学和瑞典卡罗林斯卡医学院的一项新的研究证实。现在在<em>Cell Reports</em>杂志上刊登的一篇文章报告论证了昼夜节律的中断会立即抑制斑马鱼胚胎体内血管的生长。
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昼夜节律的破坏会影响体内血管的生长，从而导致如糖尿病、肥胖和癌症等的发生，据瑞典林雪平大学和瑞典卡罗林斯卡医学院的一项新的研究证实。现在在<em>Cell Reports</em>杂志上刊登的一篇文章报告论证了昼夜节律的中断会立即抑制斑马鱼胚胎体内血管的生长。
<p align="center"><img src="http://www.bioon.com/biology/UploadFiles/201208/2012082910093797.jpg" alt="" width="500" height="467" border="0" /></p>
Yihai Cao教授领导的研究小组的突破点是一个已经被证明的非常重要的信号物质即血管内皮生长因子（VEGF）。这种物质的形成需要一个正常的生理节律。在只存活几小时之久的斑马鱼胚胎实验中，研究人员通过调节黑暗到恒光照明条件的不断变化操纵胚胎的昼夜节律。
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接着，研究人员考察了各组的血管生长。结果表明，暴露于恒光下的斑马鱼胚胎其血管的生长明显受损，另外，调节生物钟的基因的表达也受到了相应的影响。
林雪平大学（LIU）心血管生理学研究人员Lasse Dahl Jensen说：这项最新研究的结果绝对具有临床意义。昼夜节律被扰乱的人例如在工照明下工作的人、晚上轮班工人、睡眠障碍的人应该警惕昼夜节律混乱导致血管破坏性疾病风险的增加。
这些疾病包括心脏病发作、中风、慢性炎症和癌症。血管生长的破坏也影响胎儿的发育、妇女的生殖周期以及伤口的愈合。
<img src="http://www.bioon.com/biology/UploadFiles/201208/2012082910090416.gif" alt="" width="115" height="150" border="0" />
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<a title="" href="http://dx.doi.org/10.1016/j.celrep.2012.07.005" target="_blank">doi:10.1016/j.celrep.2012.07.005</a>
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<br/><strong>Opposing Effects of Circadian Clock Genes Bmal1 and Period2 in Regulation of VEGF-Dependent Angiogenesis in Developing Zebrafish </strong><br/>
Jensen LD, Cao Z, Nakamura M, Yang Y, Brutigam L, Andersson P, Zhang Y, Wahlberg E, L?nne T, Hosaka K, Cao Y.
Molecular mechanisms underlying circadian-regulated physiological processes remain largely unknown. Here, we show that disruption of the circadian clock by both constant exposure to light and genetic manipulation of key genes in zebrafish led to impaired developmental angiogenesis. A bmal1-specific morpholino inhibited developmental angiogenesis in zebrafish embryos without causing obvious nonvascular phenotypes. Conversely, a period2 morpholino accelerated angiogenic vessel growth, suggesting that Bmal1 and Period2 display opposing angiogenic effects. Using a promoter-reporter system consisting of various deleted vegf-promoter mutants, we show that Bmal1 directly binds to and activates the vegf promoter via E-boxes. Additionally, we provide evidence that knockdown of Bmal1 leads to impaired Notch-inhibition-induced vascular sprouting. These results shed mechanistic insight on the role of the circadian clock in regulation of developmental angiogenesis, and our findings may be reasonably extended to other types of physiological or pathological angiogenesis.
<br/>来源：生物谷
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</div>
</div>
<p align="center"><img src="http://www.bioon.com/biology/UploadFiles/201208/2012082910093797.jpg" alt="" width="500" height="467" border="0" /></p>
Yihai Cao教授领导的研究小组的突破点是一个已经被证明的非常重要的信号物质即血管内皮生长因子（VEGF）。这种物质的形成需要一个正常的生理节律。在只存活几小时之久的斑马鱼胚胎实验中，研究人员通过调节黑暗到恒光照明条件的不断变化操纵胚胎的昼夜节律。
<!--more-->
接着，研究人员考察了各组的血管生长。结果表明，暴露于恒光下的斑马鱼胚胎其血管的生长明显受损，另外，调节生物钟的基因的表达也受到了相应的影响。
林雪平大学（LIU）心血管生理学研究人员Lasse Dahl Jensen说：这项最新研究的结果绝对具有临床意义。昼夜节律被扰乱的人例如在工照明下工作的人、晚上轮班工人、睡眠障碍的人应该警惕昼夜节律混乱导致血管破坏性疾病风险的增加。
这些疾病包括心脏病发作、中风、慢性炎症和癌症。血管生长的破坏也影响胎儿的发育、妇女的生殖周期以及伤口的愈合。
<img src="http://www.bioon.com/biology/UploadFiles/201208/2012082910090416.gif" alt="" width="115" height="150" border="0" />
<div id="ztload">
<div>
<div>
<a title="" href="http://dx.doi.org/10.1016/j.celrep.2012.07.005" target="_blank">doi:10.1016/j.celrep.2012.07.005</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Opposing Effects of Circadian Clock Genes Bmal1 and Period2 in Regulation of VEGF-Dependent Angiogenesis in Developing Zebrafish </strong><br/>
Jensen LD, Cao Z, Nakamura M, Yang Y, Brutigam L, Andersson P, Zhang Y, Wahlberg E, L?nne T, Hosaka K, Cao Y.
Molecular mechanisms underlying circadian-regulated physiological processes remain largely unknown. Here, we show that disruption of the circadian clock by both constant exposure to light and genetic manipulation of key genes in zebrafish led to impaired developmental angiogenesis. A bmal1-specific morpholino inhibited developmental angiogenesis in zebrafish embryos without causing obvious nonvascular phenotypes. Conversely, a period2 morpholino accelerated angiogenic vessel growth, suggesting that Bmal1 and Period2 display opposing angiogenic effects. Using a promoter-reporter system consisting of various deleted vegf-promoter mutants, we show that Bmal1 directly binds to and activates the vegf promoter via E-boxes. Additionally, we provide evidence that knockdown of Bmal1 leads to impaired Notch-inhibition-induced vascular sprouting. These results shed mechanistic insight on the role of the circadian clock in regulation of developmental angiogenesis, and our findings may be reasonably extended to other types of physiological or pathological angiogenesis.
<br/>来源：生物谷
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</div>
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