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Altered expression of the natriuretic peptide system in genetically modified heme oxygenase-1 mice treated with high dietary salt

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Abstract

Heme oxygenase-1 (HO-1) has been well established as a cytoprotective molecule, and has been shown to exert cardioprotective effects in both hypertension and cardiac hypertrophy. However, the precise mechanism of the cardioprotective effect of HO-1 has yet to be fully elucidated. With the natriuretic peptide system (NPS) as a key player in cardiovascular homeostasis and tissue dynamics, we sought to examine the effect of high dietary salt treatment in genetic models of HO-1 expression, and assessed the expression of the NPS in the left ventricle (LV), to determine if the effects of altered HO-1 expression may be due to modified levels of the NPS. Age-matched 12-week old male HO-1 knockout (HO-1−/−) and HO-1 cardiomyocyte-specific transgenic overexpressing (HO-1Tg) mice were treated with either normal salt (NS; 0.8%) or high salt (HS; 8.0%) chow for 5 weeks. LV mRNA expression was determined using quantitative real-time PCR. ANP peptide level was measured in the LV and plasma using radioimmunoassay, and LV cyclic 3′-5′ guanosine monophosphate level was measured using an enzyme immunoassay kit. HO-1−/− fed HS diet had significantly higher left ventricle-to-body weight ratio (LV/BW) compared to HO-1+/+ mice fed NS diet. HO-1−/− mice had significantly reduced expression of the NPS compared to controls, and these mice did not exhibit a salt-induced increase in ANP expression. HS treatment had no noticeable effect on LV/BW in HO-1Tg mice compared to controls. HO-1Tg mice had significantly higher ANP and BNP expression compared to controls. There were no differences in LV cGMP levels among all genotypes and dietary treatments. HO-1 ablation resulted in significantly lower mRNA expression of the NPS, whereas HO-1 overexpression resulted in higher mRNA expression of the NPS. Both were substantiated by peptide levels as measured by RIA. These data indicate that the detrimental effect of reduced HO-1 expression and the cardioprotective effect of increased HO-1 expression may be due, in part, to altered expression of the NPS.

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Acknowledgments

The authors thanked the generosity of Dr. Shaw-Fang Yet of the National Health Research Institutes, Taiwan for the provision and permission of using her HO-1−/− and HO-1Tg mice for the current study. DWJA was supported by a Master’s Studentship Award from the Heart and Stroke Foundation of Ontario. Financial support from the Heart and Stroke Foundation of Ontario to SCP (Grant #: T-6108) and LGM (Grant #: NS 5520) and the Canadian Institutes of Health Research to LGM (Grant #: MOP 60500) is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Queen’s University, Room 850 Botterell Hall, Kingston, ON, K7L 3N6, Canada

    David W. J. Armstrong, M. Yat Tse & Stephen C. Pang

  2. Department of Physiology, Queen’s University, Kingston, ON, K7L 3N6, Canada

    Luis G. Melo

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  1. David W. J. Armstrong
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  2. M. Yat Tse
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Correspondence to Stephen C. Pang.

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Armstrong, D.W.J., Tse, M.Y., Melo, L.G. et al. Altered expression of the natriuretic peptide system in genetically modified heme oxygenase-1 mice treated with high dietary salt. Mol Cell Biochem 346, 57–67 (2011). https://doi.org/10.1007/s11010-010-0591-6

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  • DOI: https://doi.org/10.1007/s11010-010-0591-6

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