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Alterations in the estrogen receptor profile of cardiovascular tissues during aging

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Abstract

Estrogen exerts protective effects on the cardiovascular system via three known estrogen receptors: alpha (ERα), beta (ERß), and the G protein-coupled estrogen receptor (GPER). Our laboratory has previously showed the importance of GPER in the beneficial cardiovascular effects of estrogen. Since clinical studies indicate that the protective effects of exogenous estrogen on cardiovascular function are attenuated or reversed 10 years post-menopause, the hypothesis was that GPER expression may be reduced during aging. Vascular reactivity and GPER protein expression were assessed in female mice of varying ages. Physiological parameters, blood pressure, and estrogen receptor transcripts via droplet digital PCR (ddPCR) were assessed in the heart, kidney, and aorta of adult, middle-aged, and aged male and female C57BL/6 mice. Vasodilation to estrogen (E2) and the GPER agonist G-1 were reduced in aging female mice and were accompanied by downregulation of GPER protein. However, ERα and GPER were the predominant receptors in all tissues, whereas ERß was detectable only in the kidney. Female sex was associated with higher mRNA for both ERα and GPER in both the aorta and the heart. Aging impacted receptor transcript in a tissue-dependent manner. ERα transcript decreased in the heart with aging, while GPER expression increased in the heart. These data indicate that aging impacts estrogen receptor expression in the cardiovascular system in a tissue- and sex-specific manner. Understanding the impact of aging on estrogen receptor expression is critical for developing selective hormone therapies that protect from cardiovascular damage.

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Funding

This research was funded by National Institutes Of Health, National Heart, Lung, and Blood Institute, HL133619, National Institutes of General Medical Sciences, P30GM103337 and U54GM104940, National Institute of Diabetes and Digestive and Kidney Diseases, DK107694, National Institute of Neurological Disorders and Stroke and National Institute of General Medical Sciences NS094834, and National Institute on Aging, AG047296.

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Authors and Affiliations

  1. Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, 70112, USA

    Rakesh Gurrala, Isabella M. Kilanowski-Doroh, Dillion D. Hutson, Benard O. Ogola, Margaret A. Zimmerman, Prasad V. G. Katakam, Ricardo Mostany & Sarah H. Lindsey

  2. Department of Physiology, Tulane University School of Medicine, New Orleans, LA, 70112, USA

    Ryousuke Satou & Sarah H. Lindsey

  3. Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, LA, 7011, USA

    Ryousuke Satou & Sarah H. Lindsey

  4. Tulane Brain Institute, Tulane University, New Orleans, LA, 70112, USA

    Prasad V. G. Katakam, Ricardo Mostany & Sarah H. Lindsey

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  1. Rakesh Gurrala
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  3. Dillion D. Hutson
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  4. Benard O. Ogola
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Rakesh Gurrala, Dillion Hutson, Isabella Kilanowski-Doroh, and Sarah Lindsey. The first draft of the manuscript was written by Rakesh Gurrala and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Sarah H. Lindsey.

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Rakesh Gurrala and Isabella M. Kilanowski-Doroh are the co-first authors.

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Gurrala, R., Kilanowski-Doroh, I.M., Hutson, D.D. et al. Alterations in the estrogen receptor profile of cardiovascular tissues during aging. GeroScience 43, 433–442 (2021). https://doi.org/10.1007/s11357-021-00331-3

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