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Cardiovascular rhythms and the molec...

Westgate, Elizabeth Jeanne.

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Cardiovascular rhythms and the molecular clock.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Cardiovascular rhythms and the molecular clock./
作者:	Westgate, Elizabeth Jeanne.
面頁冊數:	121 p.
附註:	Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2281.
Contained By:	Dissertation Abstracts International68-04B.
標題:	Health Sciences, Pharmacology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3261007

Cardiovascular rhythms and the molecular clock.
Westgate, Elizabeth Jeanne.

Cardiovascular rhythms and the molecular clock. - 121 p.

Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2281.

Thesis (Ph.D.)--University of Pennsylvania, 2007.

Cardiovascular physiology, as well as path ophysiology, undergoes marked diurnal variation, which may be influenced by the master circadian clock located in the suprachiasmatic nucleus. Peripheral clocks have recently been discovered in several tissues including heart, aorta, and aortic smooth muscle, and a mechanism by which the latter clock may be phase shifted by circulating hormones elucidated. However, no study to date has characterized a clock in isolated vascular endothelium or examined the ability of hormones to phase shift an endothelial clock. We examined the expression of core clock proteins in vascular endothelium by Western blot. The ability of serum shock or humoral treatment to induce clock gene expression in these cells was also examined. Although endothelial cells expressed the necessary components for a functional oscillator, these cells did not respond to the serum shock model via rhythmic expression of molecular clock components. Humoral factors failed to alter acutely the expression of clock genes in these cells. The expression of clock- or endothelial-specific genes in aortas harvested from Bmal1-ECKO (endothelial cell knock-out) mice was analyzed, providing some of the first in vivo evidence for endothelial clock regulation by BMAL1. Microarray analysis of mouse aorta harvested across circadian time had previously revealed oscillations in transcripts relevant to vascular injury and integrity. We explored the influence of circadian clocks in conditioning the response to vascular injury using an in vivo photochemical injury model. A diurnal variation in the time to vessel occlusion was observed in WT mice and this pattern was disrupted with clock dysfunction. Clock-mutant and Npas2 knock-out mice displayed significantly longer occlusion times compared to WT, while loss of endothelial Bmal1 had the opposite impact. Platelet activation or aggregation does not appear to impact the diurnal regulation of thrombogenesis. The fibrinolytic system may play a role, although diurnal variations in fibrinolysis alone do not fully explain the observed phenomena. Future studies will likely shed light on the multiple mechanisms and complex interplay involved.Subjects--Topical Terms:

1017717
Health Sciences, Pharmacology.

Cardiovascular rhythms and the molecular clock.
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