{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:47:38Z","timestamp":1790207258095,"version":"4.1.0"},"reference-count":88,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T00:00:00Z","timestamp":1737158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Hypertension is one of the most common comorbidities in cardiometabolic diseases, affecting nearly one third of adults. As a result, its pathophysiological mechanisms have been studied extensively and are focused around pressure natriuresis, the renin\u2013angiotensin system (RAS), the sympathetic nervous system, oxidative stress, and endothelial dysfunction. Additionally, hypertension secondary to other underlying etiologies also exists. While clinical evidence has clearly shown differences in hypertension development in males and females, relatively little is known about the pathophysiological mechanisms behind these differences. Sex hormones likely play a key role, as they modulate many factors related to hypertension development. In this review, we postulate the potential role for sexually dimorphic fat metabolism in the physiology of hypertension. In brief, estrogen promotes subcutaneous fat deposition over visceral fat and increases in mass via adaptive hyperplasia rather than pathogenic hypertrophy. This adipose tissue subsequently produces anti-inflammatory effects and inhibits metabolic dysfunction-associated fatty liver disease (MAFLD) and RAS activation, ultimately leading to decreased levels of hypertension in pre-menopausal females. On the other hand, androgens and the lack of estrogens promote visceral and ectopic fat deposition, including in the liver, and lead to increased circulating pro-inflammatory cytokines and potentially subsequent RAS activation and hypertension development in males and post-menopausal females. Understanding the sex-specific differences in fat metabolism may provide deeper insights into the patho-mechanisms associated with hypertension and lead to more comprehensive sex-specific care.<\/jats:p>","DOI":"10.3390\/biom15010143","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T04:04:12Z","timestamp":1737345852000},"page":"143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Sex-Specific Differences in the Pathophysiology of Hypertension"],"prefix":"10.3390","volume":"15","author":[{"given":"Hannah","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, St. Boniface Hospital Albrechtsen Research Centre, Institute of Cardiovascular Sciences, Rady College of Medicine, Max Rady Faculty of Health Sciences, University of Manitoba, Rm. 3042, 351 Tach\u00e9 Avenue, Winnipeg, MB R2H 2A6, Canada"},{"name":"Department of Pharmacology and Therapeutics, St. Boniface Hospital Albrechtsen Research Centre, Institute of Cardiovascular Sciences, Rady College of Medicine, Max Rady Faculty of Health Sciences, University of Manitoba, Rm. 3042, 351 Tach\u00e9 Avenue, Winnipeg, MB R2H 2A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawan K.","family":"Singal","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, St. Boniface Hospital Albrechtsen Research Centre, Institute of Cardiovascular Sciences, Rady College of Medicine, Max Rady Faculty of Health Sciences, University of Manitoba, Rm. 3042, 351 Tach\u00e9 Avenue, Winnipeg, MB R2H 2A6, Canada"},{"name":"Department of Pharmacology and Therapeutics, St. Boniface Hospital Albrechtsen Research Centre, Institute of Cardiovascular Sciences, Rady College of Medicine, Max Rady Faculty of Health Sciences, University of Manitoba, Rm. 3042, 351 Tach\u00e9 Avenue, Winnipeg, MB R2H 2A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6663-1225","authenticated-orcid":false,"given":"Amir","family":"Ravandi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, St. Boniface Hospital Albrechtsen Research Centre, Institute of Cardiovascular Sciences, Rady College of Medicine, Max Rady Faculty of Health Sciences, University of Manitoba, Rm. 3042, 351 Tach\u00e9 Avenue, Winnipeg, MB R2H 2A6, Canada"},{"name":"Department of Pharmacology and Therapeutics, St. Boniface Hospital Albrechtsen Research Centre, Institute of Cardiovascular Sciences, Rady College of Medicine, Max Rady Faculty of Health Sciences, University of Manitoba, Rm. 3042, 351 Tach\u00e9 Avenue, Winnipeg, MB R2H 2A6, Canada"},{"name":"Section of Cardiology, Department of Medicine, Rady College of Medicine, Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R2H 2A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Rabinovich-Nikitin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, St. Boniface Hospital Albrechtsen Research Centre, Institute of Cardiovascular Sciences, Rady College of Medicine, Max Rady Faculty of Health Sciences, University of Manitoba, Rm. 3042, 351 Tach\u00e9 Avenue, Winnipeg, MB R2H 2A6, Canada"},{"name":"Department of Pharmacology and Therapeutics, St. Boniface Hospital Albrechtsen Research Centre, Institute of Cardiovascular Sciences, Rady College of Medicine, Max Rady Faculty of Health Sciences, University of Manitoba, Rm. 3042, 351 Tach\u00e9 Avenue, Winnipeg, MB R2H 2A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1161\/CIRCULATIONAHA.115.018912","article-title":"Global Disparities of Hypertension Prevalence and Control","volume":"134","author":"Mills","year":"2016","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.cpcardiol.2007.01.002","article-title":"Systemic hypertension","volume":"32","author":"Elliott","year":"2007","journal-title":"Curr. 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