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Clock genes: involvement in the control of blood pressure

English title Clock genes: involvement in the control of blood pressure
Applicant Antic Vladan
Number 105900
Funding scheme Project funding
Research institution Division de Physiologie Département de Médecine Université de Fribourg
Institution of higher education University of Fribourg - FR
Main discipline Cardiovascular Research
Start/End 01.10.2004 - 31.07.2007
Approved amount 167'000.00
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Keywords (4)

clock genes; cardiovascular disease; hypertension; endothelial dysfunctionn

Lay Summary (English)

Lead
Lay summary
Lay summary for the project Nr. 105900 "Clock genes: involvement in the control of blood pressure" of Vladan Antic (text elaborated by Jean-Pierre Montani, after the departure of Dr Antic for the pharmaceutical industry two years after beginning the grant)Most of the physiological parameters follow circadian rhythms, which are autonomous recurrent rhythms of about 24 hours. Circadian rhythms are orchestrated by clock genes expressed in particular in a brain center, the suprachiasmatic nucleus, that influences the autonomic nervous system and the cardiovascular system, leading thereby to circadian fluctuations in blood pressure and heart rate. Alterations of the circadian blood pressure pattern are frequently observed in hypertension, leading to higher incidence of target-organ damage. There are few studies investigating possible implications of clock genes in the control of blood pressure, and none have considered the role of mPer2 gene, a key component of the molecular circadian clock. To address this question, we instrument adult male mice lacking the mPer2 gene and wild type controls with telemetry implants for continuous hemodynamic recording 24h a day. Our studies provide evidence that mice lacking a functional clock gene mPer2 show a disturbed hemodynamic circadian rhythm, with lower night-day differences in arterial pressure and heart rate, although the light cue is very effective in inducing circardian rhythms. Interestingly, mutation in the Per2 gene in mice is associated with aortic endothelial dysfunction but does not, however, elevate blood pressure. Together, these projects provide information on the mechanisms by which clock genes are implicated in the coordination of the cardiovascular circadian rhythms, and information on the involvement of endogenous clock machinery in the development of cardiovascular pathology.
Direct link to Lay Summary Last update: 21.02.2013

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