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Altered Expression of the Natriuretic Peptide System in Genetically Modified Heme Oxygenase-1 Mice Treated with High Dietary Salt

Overview
Publisher Springer
Specialty Biochemistry
Date 2010 Sep 28
PMID 20872048
Citations 2
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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-1(Tg)) 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-1(Tg) mice compared to controls. HO-1(Tg) 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.

Citing Articles

Salt-Sensitive Ileal Microbiota Plays a Role in Atrial Natriuretic Peptide Deficiency-Induced Cardiac Injury.

Li S, Chen S, Nie M, Wen L, Zou B, Zhang L Nutrients. 2022; 14(15).

PMID: 35956306 PMC: 9370783. DOI: 10.3390/nu14153129.


Gestational hypertension and the developmental origins of cardiac hypertrophy and diastolic dysfunction.

Armstrong D, Tse M, Wong P, M Ventura N, Meens J, Johri A Mol Cell Biochem. 2014; 391(1-2):201-9.

PMID: 24718734 DOI: 10.1007/s11010-014-2003-9.

References
1.
Tsujita Y, Muraski J, Shiraishi I, Kato T, Kajstura J, Anversa P . Nuclear targeting of Akt antagonizes aspects of cardiomyocyte hypertrophy. Proc Natl Acad Sci U S A. 2006; 103(32):11946-51. PMC: 1567678. DOI: 10.1073/pnas.0510138103. View

2.
Liu X, Pachori A, Ward C, Davis J, Gnecchi M, Kong D . Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function. FASEB J. 2006; 20(2):207-16. DOI: 10.1096/fj.05-4435com. View

3.
Liu X, Simpson J, Brunt K, Ward C, Hall S, Kinobe R . Preemptive heme oxygenase-1 gene delivery reveals reduced mortality and preservation of left ventricular function 1 yr after acute myocardial infarction. Am J Physiol Heart Circ Physiol. 2007; 293(1):H48-59. DOI: 10.1152/ajpheart.00741.2006. View

4.
Shiraishi I, Melendez J, Ahn Y, Skavdahl M, Murphy E, Welch S . Nuclear targeting of Akt enhances kinase activity and survival of cardiomyocytes. Circ Res. 2004; 94(7):884-91. DOI: 10.1161/01.RES.0000124394.01180.BE. View

5.
Takimoto E, Champion H, Li M, Belardi D, Ren S, Rodriguez E . Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med. 2005; 11(2):214-22. DOI: 10.1038/nm1175. View