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Publication : Corticosteroids Are Essential for Maintaining Cardiovascular Function in Male Mice.

First Author  Cruz-Topete D Year  2016
Journal  Endocrinology Volume  157
Issue  7 Pages  2759-71
PubMed ID  27219275 Mgi Jnum  J:239767
Mgi Id  MGI:5829619 Doi  10.1210/en.2015-1604
Citation  Cruz-Topete D, et al. (2016) Corticosteroids Are Essential for Maintaining Cardiovascular Function in Male Mice. Endocrinology 157(7):2759-71
abstractText  Activation of the hypothalamic-pituitary-adrenal axis results in the release of hormones from the adrenal glands, including glucocorticoids and mineralocorticoids. The physiological association between corticosteroids and cardiac disease is becoming increasingly recognized; however, the mechanisms underlying this association are not well understood. To determine the biological effects of corticosteroids on the heart, we investigated the impact of adrenalectomy in C57BL/6 male mice. Animals were adrenalectomized (ADX) at 1 month of age and maintained for 3-6 months after surgery to evaluate the effects of long-term adrenalectomy on cardiac function. Morphological evaluation suggested that ADX mice showed significantly enlarged hearts compared with age-matched intact controls. These changes in morphology correlated with deficits in left ventricular (LV) function and electrocardiogram (ECG) abnormalities in ADX mice. Correlating with these functional defects, gene expression analysis of ADX hearts revealed aberrant expression of a large cohort of genes associated with cardiac hypertrophy and arrhythmia. Combined corticosterone and aldosterone replacement treatment prevented the emergence of cardiac abnormalities in ADX mice, whereas corticosterone replacement prevented the effects of adrenalectomy on LV function but did not block the emergence of ECG alterations. Aldosterone replacement did not preserve the LV function but prevented ECG abnormalities. Together, the data indicate that adrenal glucocorticoids and mineralocorticoids either directly or indirectly have selective effects in the heart and their signaling pathways are essential in maintaining normal cardiac function.
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