Aromatase deficiency confers paradoxical postischemic cardioprotection

Bell, James R., Mellor, Kimberley M., Wollermann, Amanda C., Ip, Wendy T. K., Reichelt, Melissa E., Meachem, Sarah J., Simpson, Evan R. and Delbridge, Lea M. D. (2011) Aromatase deficiency confers paradoxical postischemic cardioprotection. Endocrinology, 152 12: 4937-4947. doi:10.1210/en.2011-1212

Author Bell, James R.
Mellor, Kimberley M.
Wollermann, Amanda C.
Ip, Wendy T. K.
Reichelt, Melissa E.
Meachem, Sarah J.
Simpson, Evan R.
Delbridge, Lea M. D.
Title Aromatase deficiency confers paradoxical postischemic cardioprotection
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
Publication date 2011-12-01
Year available 2011
Sub-type Article (original research)
DOI 10.1210/en.2011-1212
Open Access Status Not yet assessed
Volume 152
Issue 12
Start page 4937
End page 4947
Total pages 11
Place of publication Chevy Chase, MD, United States
Publisher The Endocrine Society
Language eng
Formatted abstract
The conventional view is that estrogen confers female cardioprotection. Estrogen synthesis depends on androgen availability, with aromatase regulating conversion of testosterone to estradiol. Extragonadal aromatase expression mediates estrogen production in some tissues, but a role for local steroid conversion has not yet been demonstrated in the heart. This study's goal was to investigate how aromatase deficiency influences myocardial function and ischemic resilience. RT-PCR analysis of C57Bl/6 mouse hearts confirmed cardiac-specific aromatase expression in adult females. Functional performance of isolated hearts from female aromatase knockout (ArKO) and aromatase wild-type mice were compared. Left ventricular developed pressures were similar in aerobic perfusion, but the maximal rate of rise of ventricular pressure was modestly reduced in ArKOhearts (3725 ± 144 vs. 4272 ± 154 mm Hg/sec, P < 0.05). After 25 min of ischemia, the recovery of left ventricular developed pressure was substantially improved in ArKO (percentage of basal at 60 min of reperfusion, 62 ± 8 vs. 30± 6%; P < 0.05). Hypercontracture was attenuated (end diastolic pressure, 25 ±5 vs. 51 ± 1 mm Hg; P < 0.05), and lactate dehydrogenase content of coronary effluent was reduced throughout reperfusion in ArKO hearts. This was associated with a hyperphosphorylation of phospholamban and a reduction in phosphorylated Akt. Immediately after reperfusion, ArKO hearts exhibited increased incidence of ventricular premature beats (194 ± 70 vs. 46 ± 6, P < 0.05). These observations indicate more robust functional recovery, reduced cellular injury, and modified cardiomyocyte Ca2+ handling in aromatase-deficient hearts. Our findings indicate that androgen-to-estrogen conversion may be of pathophysiologic importance to the heart and challenge the notion that estrogen deficiency is deleterious. These studies suggest the possibility that aromatase suppression may offer inotropic benefit in the acute ischemia/reperfusion setting with appropriate arrhythmia management.
Keyword Endocrinology & Metabolism
Endocrinology & Metabolism
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
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