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J Chalmers, Physiology, University of Toronto, Toronto, Ontario, Canada
S Lin, Physiology, University of Toronto, Toronto, Ontario, Canada
T Martino, Physiology, University of Toronto, Toronto, Ontario, Canada
S Arab, Heart and Stroke/Richard Lewar Centre of Excellence for Cardiovascular Research, Toronto General Hospital Research Institute, Toronto, Ontario, Canada
P Liu, Heart and Stroke/Richard Lewar Centre of Excellence for Cardiovascular Research, Toronto General Hospital Research Institute, Toronto, Ontario, Canada
M Husain, Heart and Stroke/Richard Lewar Centre of Excellence for Cardiovascular Research, Toronto General Hospital Research Institute, Toronto, Ontario, Canada
M Sole, Heart and Stroke/Richard Lewar Centre of Excellence for Cardiovascular Research, Toronto General Hospital Research Institute, Toronto, Ontario, Canada
D Belsham, Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada

Correspondence: Denise Belsham, Email: d.belsham{at}utoronto.ca

Abstract

Neuroendocrine peptides express biologic activity relevant to the cardiovascular system, including regulating heart rate and blood pressure, though little is known about the mechanisms involved. Here we investigated neuroendocrine gene expression underlying diurnal physiology of the heart. We first used microarray and RT-PCR analysis and demonstrate the simultaneous expression of neuroendocrine genes in normal murine heart, including proopiomelanocortin (POMC), gonadotropin-releasing hormone (GnRH), neuropeptide Y (NPY), leptin receptor (ObRb), growth hormone-releasing hormone (GHRH), cocaine and amphetamine-regulated transcript (CART), proglucagon, and galanin. We examined diurnal gene expression profiles, with cosinar bioinformatics to evaluate statistically significant rhythms. The POMC gene exhibits a day/night, circadian or diurnal, pattern of expression in heart, and we postulated that this may be important to cardiac growth and renewal. POMC diurnal gene rhythmicity is altered in pressure-overload cardiac hypertrophy, as compared to control heart, and levels increased at the dark-to-light transition times. These findings are also consistent with the proposal that neuropeptides mediate adverse remodelling processes, such as occur in pathologic hypertrophy. To investigate cellular responses, we screened three cell lines representing fibroblasts, cardiac myocytes, and vascular smooth muscle cells (NIH3T3, HL-1 and Movas-1, respectively). POMC mRNA expression is most notable in Movas-1 cells, and furthermore, exhibits rhythmicity with culture synchronization. Taken together, these results highlight the diverse neuroendocrine mRNA expression profiles in cardiovasculature, and provide a novel model vascular culture system to research the role these neuropeptides play in organ health, integrity, and disease.

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				M. J. Sole and T. A. Martino Diurnal physiology: core principles with application to the pathogenesis, diagnosis, prevention, and treatment of myocardial hypertrophy and failure J Appl Physiol, October 1, 2009; 107(4): 1318 - 1327. [Abstract] [Full Text] [PDF]