BES2003 Poster Presentations Steroids (39 abstracts)
Aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) gene expression in the normal and failing rat heart
CA Millar 1 , P Ye 1 , GA Gray 2 , AF Wallace 2 , SM MacKenzie 1 , R Fraser 1 , JMC Connell 1 & E Davies 1
1MRC Blood Pressure Group, Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK; 2Centre for Cardiovascular Science, University of Edinburgh, School of Biomedical and Clinical Laboratory Science, Edinburgh, UK.
Aldosterone synthase and 11beta-hydroxylase catalyse the final steps of glucocorticoid (corticosterone) and mineralocorticoid (aldosterone) production in the rat adrenal cortex. They are encoded by the CYP11B2 and CYP11B2 genes respectively. Recent studies have shown that CYP11B1 and CYP11B2 are also expressed in the brain, the vascular system and the heart where it has been suggested that aldosterone influences cardiac function and plays a role in cardiac fibrosis. However, it is unclear if the aldosterone is produced locally in the heart or is derived from the adrenal gland. In this study, we have measured CYP11B2 and CYP11B1 expression in the adrenal gland and cardiac tissue in rats with heart failure.
Heart failure (HF) was induced in male Wistar rats (n=3) by coronary artery ligation Sham operated animals (n=3) were used as controls. RNA was isolated from the adrenal gland, ventricles and septum 15 weeks post-operatively. CYP11B2 and CYP11B1 expression were measured by real-time quantitative RT-PCR using a LightCycler.
Heart failure had no effect on CYP11B1 expression, which was 7.8x108 plus/minus 2.8x108 and 3.5x108 plus/minus 1.1x108 copies/microgram RNA in the sham and HF rats respectively. Similarly, there was no effect on adrenal CYP11B2 expression which was 1.2x107 plus/minus 2.9x106 and 1.2x107 plus/minus 1.3x106 copies/microgram RNA in the sham and HF rats respectively. CYP11B1 and CYP11B2 expression in the sham and HF heart was never greater than 102 copies/microgram RNA and was therefore too low to be detected reproducibly.
CYP11B1 and CYP11B2 expression can be quantified precisely in adrenal tissue. However, under normal physiological conditions, the levels of CYP11B1 and CYP11B2 gene expression in the heart are effectively non-detectable. CYP11B2 expression did not increase in the animals with heart failure, suggesting that aldosterone does not play a role in this model of heart failure where there is little or no evidence of cardiac fibrosis.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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