دورية أكاديمية
Salt Sensitivity of Blood Pressure and Aldosterone: Interaction Between the Lysine-specific Demethylase 1 Gene, Sex, and Age.
| العنوان: | Salt Sensitivity of Blood Pressure and Aldosterone: Interaction Between the Lysine-specific Demethylase 1 Gene, Sex, and Age. |
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| المؤلفون: | Parksook WW; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.; Department of Medicine (Division of Endocrinology and Metabolism, and Division of General Internal Medicine), Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand., Heydarpour M; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA., Gholami SK; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA., Luther JM; Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Vanderbilt Hypertension Center, Nashville, Tennessee 37232, USA., Hopkins PN; Cardiovascular Genetics Research Unit, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA., Pojoga LH; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA., Williams JS; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. |
| المصدر: | The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2022 Apr 19; Vol. 107 (5), pp. 1294-1302. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375362 Publication Model: Print Cited Medium: Internet ISSN: 1945-7197 (Electronic) Linking ISSN: 0021972X NLM ISO Abbreviation: J Clin Endocrinol Metab Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2017- : New York : Oxford University Press Original Publication: Springfield, Ill. : Charles C. Thomas |
| مواضيع طبية MeSH: | Aldosterone* , Hypertension*/genetics, Animals ; Blood Pressure/genetics ; Epigenesis, Genetic ; Estrogens ; Female ; Histone Demethylases/genetics ; Histone Demethylases/metabolism ; Humans ; Lysine ; Mice ; Mice, Knockout ; Sodium Chloride, Dietary |
| مستخلص: | Context: Salt sensitivity of blood pressure (SSBP) is associated with increased cardiovascular risk, especially in individuals of African descent, although the underlying mechanisms remain obscure. Lysine-specific demethylase 1 (LSD1) is a salt-sensitive epigenetic regulator associated with SSBP and aldosterone dysfunction. An LSD1 risk allele in humans is associated with SSBP and lower aldosterone levels in hypertensive individuals of African but not European descent. Heterozygous knockout LSD1 mice display SSBP and aldosterone dysregulation, but this effect is modified by age and biological sex. This might explain differences in cardiovascular risk with aging and biological sex in humans. Objective: This work aims to determine if LSD1 risk allele (rs587618) carriers of African descent display a sex-by-age interaction with SSBP and aldosterone regulation. Methods: We analyzed 297 individuals of African and European descent from the HyperPATH cohort. We performed multiple regression analyses for outcome variables related to SSBP and aldosterone. Results: LSD1 risk allele carriers of African (but not European) descent had greater SSBP than nonrisk homozygotes. Female LSD1 risk allele carriers of African descent had greater SSBP, mainly relationship-driven by women with low estrogen (postmenopausal). There was a statistically significant LSD1 genotype-sex interaction in aldosterone response to angiotensin II stimulation in individuals aged 50 years or younger, with female carriers displaying decreased aldosterone responsiveness. Conclusion: SSBP associated with LSD1 risk allele status is driven by women with a depleted estrogen state. Mechanisms related to a resistance to develop SSBP in females are uncertain but may relate to an estrogen-modulating effect on mineralocorticoid receptor (MR) activation and/or LSD1 epigenetic regulation of the MR. (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.) |
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| معلومات مُعتمدة: | T32 HL007609 United States HL NHLBI NIH HHS; R01 HL127146 United States HL NHLBI NIH HHS; GRNT20500000 American Heart Association |
| فهرسة مساهمة: | Keywords: age; aldosterone; lysine-specific demethylase 1; salt sensitivity of blood pressure; sex |
| المشرفين على المادة: | 0 (Estrogens) 0 (Sodium Chloride, Dietary) 4964P6T9RB (Aldosterone) EC 1.14.11.- (Histone Demethylases) EC 1.14.11.- (KDM1a protein, mouse) EC 1.5.- (KDM1A protein, human) K3Z4F929H6 (Lysine) |
| تواريخ الأحداث: | Date Created: 20220113 Date Completed: 20220420 Latest Revision: 20230112 |
| رمز التحديث: | 20230112 |
| مُعرف محوري في PubMed: | PMC9016472 |
| DOI: | 10.1210/clinem/dgac011 |
| PMID: | 35022775 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1945-7197 |
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| DOI: | 10.1210/clinem/dgac011 |