Sex-Specific Differences in the Pathophysiology of Hypertension
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–angiotensin system (RAS), the sympathetic nervou...
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MDPI AG
2025-01-01
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| author | Hannah Zhang Pawan K. Singal Amir Ravandi Inna Rabinovich-Nikitin |
| author_facet | Hannah Zhang Pawan K. Singal Amir Ravandi Inna Rabinovich-Nikitin |
| author_sort | Hannah Zhang |
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| description | 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–angiotensin 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. |
| format | Article |
| id | doaj-art-c102640fed1b4d40b930cecae587cdf0 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-c102640fed1b4d40b930cecae587cdf02025-01-24T13:25:21ZengMDPI AGBiomolecules2218-273X2025-01-0115114310.3390/biom15010143Sex-Specific Differences in the Pathophysiology of HypertensionHannah Zhang0Pawan K. Singal1Amir Ravandi2Inna Rabinovich-Nikitin3Department 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 Taché Avenue, Winnipeg, MB R2H 2A6, CanadaDepartment 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 Taché Avenue, Winnipeg, MB R2H 2A6, CanadaDepartment 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 Taché Avenue, Winnipeg, MB R2H 2A6, CanadaDepartment 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 Taché Avenue, Winnipeg, MB R2H 2A6, CanadaHypertension 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–angiotensin 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.https://www.mdpi.com/2218-273X/15/1/143hypertensionfat metabolismwomensex hormones |
| spellingShingle | Hannah Zhang Pawan K. Singal Amir Ravandi Inna Rabinovich-Nikitin Sex-Specific Differences in the Pathophysiology of Hypertension Biomolecules hypertension fat metabolism women sex hormones |
| title | Sex-Specific Differences in the Pathophysiology of Hypertension |
| title_full | Sex-Specific Differences in the Pathophysiology of Hypertension |
| title_fullStr | Sex-Specific Differences in the Pathophysiology of Hypertension |
| title_full_unstemmed | Sex-Specific Differences in the Pathophysiology of Hypertension |
| title_short | Sex-Specific Differences in the Pathophysiology of Hypertension |
| title_sort | sex specific differences in the pathophysiology of hypertension |
| topic | hypertension fat metabolism women sex hormones |
| url | https://www.mdpi.com/2218-273X/15/1/143 |
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