Corticosteroids are essential for maintaining cardiovascular function in male mice

Diana Cruz-Topete, Page H. Myers, Julie F. Foley, Monte Willis, John A. Cidlowski

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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. Animalswereadrenalectomized(ADX)at1monthofageandmaintained for 3-6monthsafter 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.

Original languageEnglish (US)
Pages (from-to)2759-2771
Number of pages13
JournalEndocrinology
Volume157
Issue number7
DOIs
StatePublished - Jul 1 2016
Externally publishedYes

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Adrenalectomy
Adrenal Cortex Hormones
Left Ventricular Function
Mineralocorticoids
Electrocardiography
Cardiomegaly
Corticosterone
Aldosterone
Glucocorticoids
Adrenal Glands
Cardiac Arrhythmias
Heart Diseases
Hormones
Gene Expression
Genes

ASJC Scopus subject areas

  • Endocrinology

Cite this

Corticosteroids are essential for maintaining cardiovascular function in male mice. / Cruz-Topete, Diana; Myers, Page H.; Foley, Julie F.; Willis, Monte; Cidlowski, John A.

In: Endocrinology, Vol. 157, No. 7, 01.07.2016, p. 2759-2771.

Research output: Contribution to journalArticle

Cruz-Topete, D, Myers, PH, Foley, JF, Willis, M & Cidlowski, JA 2016, 'Corticosteroids are essential for maintaining cardiovascular function in male mice', Endocrinology, vol. 157, no. 7, pp. 2759-2771. https://doi.org/10.1210/en.2015-1604
Cruz-Topete, Diana ; Myers, Page H. ; Foley, Julie F. ; Willis, Monte ; Cidlowski, John A. / Corticosteroids are essential for maintaining cardiovascular function in male mice. In: Endocrinology. 2016 ; Vol. 157, No. 7. pp. 2759-2771.
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