TY - JOUR
T1 - Alterations in the estrogen receptor profile of cardiovascular tissues during aging
AU - Gurrala, Rakesh
AU - Kilanowski-Doroh, Isabella M.
AU - Hutson, Dillion D.
AU - Ogola, Benard O.
AU - Zimmerman, Margaret A.
AU - Katakam, Prasad V.G.
AU - Satou, Ryousuke
AU - Mostany, Ricardo
AU - Lindsey, Sarah H.
N1 - Funding Information:
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.
Publisher Copyright:
© 2021, American Aging Association.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - Aging
KW - Aromatase
KW - Cardiovascular
KW - Droplet digital PCR (ddPCR)
KW - Estrogen receptors
KW - Sex differences
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U2 - 10.1007/s11357-021-00331-3
DO - 10.1007/s11357-021-00331-3
M3 - Article
C2 - 33558965
AN - SCOPUS:85100826651
SN - 2509-2715
VL - 43
SP - 433
EP - 442
JO - GeroScience
JF - GeroScience
IS - 1
ER -