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Identifying key neuronal pathways mediating melanocortin's effects on cardiovascular function

Project information

Grant agreement ID: 46515

  • Start date

    1 March 2007

  • End date

    28 February 2009

Funded under:

FP6-MOBILITY

Coordinated by:

UNIVERSITY OF BRISTOL

United Kingdom

Objective

Population statistics demonstrate drastically increased risk of cardiovascular death with increasing body mass index. Given the current obesity epidemic our need to understand the central neuronal pathways regulating energy homeostasis and cardiovascular function could not be greater.

This proposal aims to determine key neuronal pathways mediating melanocortin's autonomic effects on cardiovascular function. It combines molecular genetics and whole animal physiology to advance translational research in the development of effective therapies against obesity-induced hypertension. Recent evidence suggests that both obesity and essential hypertension are associated with increased sympathetic nerve activity. Increased sympatho-activation in obesity-associated hypertension has been linked to increases in central signalling via the melanocortin-4-receptor (MC4R).

We hypothesize that the pressor actions of obesity are mediated via specific MC4Rs on central neurons regulating arterial blood pressure. We will investigate which subpopulation of MC4Rs mediates melanocortin's effects on cardiovascular function using functional genomics approaches, including an MC4R deficient mouse, in which a disrupted MC4R can be reactivated in specific CNS areas by the actions of Cre-recombinase. Using in vivo mouse telemetry we will thus determine the neuronal pathways involved in melanocortin-mediated regulation of cardiovascular function and define the MC4R¿s role in obesity-induced activation of the sympathetic nervous system.

This proposal is absolutely consistent with the Sixth (and future 7th) Framework Programme, placing particular emphasis on functional genomics and the combat against major diseases such as hypertension. Furthermore, it brings significant skills in state-of-the-art generation of mouse models relevant to human disease, in combination with sophisticated physiological techniques to the European Research Area, thereby increasing its attractiveness to young researchers.

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Coordinator

UNIVERSITY OF BRISTOL

Address

Senate House, Tyndall Avenue
Bristol

United Kingdom

Project information

Grant agreement ID: 46515

  • Start date

    1 March 2007

  • End date

    28 February 2009

Funded under:

FP6-MOBILITY

Coordinated by:

UNIVERSITY OF BRISTOL

United Kingdom