Sex-Specific Antioxidant and Anti-Inflammatory Protective Effects of AMPK in Cardiovascular Diseases

Cardiovascular diseases such as coronary heart disease, heart failure, or stroke are the most common cause of death worldwide and are regularly based on risk factors like diabetes mellitus, hypertension, or obesity. At the same time, both diseases and risk factors are significantly influenced by sex...

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Main Authors: Lea Strohm, Dominika Mihalikova, Alexander Czarnowski, Zita Schwaibold, Andreas Daiber, Paul Stamm
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/14/5/615
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author Lea Strohm
Dominika Mihalikova
Alexander Czarnowski
Zita Schwaibold
Andreas Daiber
Paul Stamm
author_facet Lea Strohm
Dominika Mihalikova
Alexander Czarnowski
Zita Schwaibold
Andreas Daiber
Paul Stamm
author_sort Lea Strohm
collection DOAJ
description Cardiovascular diseases such as coronary heart disease, heart failure, or stroke are the most common cause of death worldwide and are regularly based on risk factors like diabetes mellitus, hypertension, or obesity. At the same time, both diseases and risk factors are significantly influenced by sex hormones. In order to better understand this influence and also specifically improve the therapy of female patients, medical research has recently focused increasingly on gender-specific differences. The goal is to develop personalized, gender-specific therapy concepts for these diseases to further enhance health outcomes. The enzyme adenosine monophosphate-activated protein kinase (AMPK) is a central regulator of energy metabolism, protecting the cardiovascular system from energy depletion, thereby promoting vascular health and preventing cellular damage. AMPK confers cardioprotective effects by preventing endothelial and vascular dysfunction, and by controlling or regulating oxidative stress and inflammatory processes. For AMPK, sex-specific effects were reported, influencing metabolic and cardiovascular responses. Exercise and metabolic stress generally cause higher AMPK activity in males. At the same time, females exhibit protective mechanisms against insulin resistance or oxidative stress, particularly in conditions like obesity. Additionally, males subject to AMPK deficiency seem to experience greater cardiac and mitochondrial dysfunction. In contrast, females show improvement in cardiovascular function after pharmacological AMPK activation. These differences, influenced by hormones, body composition, and gene expression, highlight the potential to develop personalized, sex-specific AMPK-targeted therapeutic strategies for cardiovascular diseases in the future. Here, we discuss the most actual scientific background, focusing on the protective, gender-specific effects of AMPK, and highlight potential clinical applications.
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spelling doaj-art-c9a99eb0d5f24beda05877bdbf4abe6b2025-08-20T03:14:39ZengMDPI AGAntioxidants2076-39212025-05-0114561510.3390/antiox14050615Sex-Specific Antioxidant and Anti-Inflammatory Protective Effects of AMPK in Cardiovascular DiseasesLea Strohm0Dominika Mihalikova1Alexander Czarnowski2Zita Schwaibold3Andreas Daiber4Paul Stamm5Department of Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, GermanyDepartment of Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, GermanyDepartment of Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, GermanyDepartment of Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, GermanyDepartment of Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, GermanyDepartment of Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, GermanyCardiovascular diseases such as coronary heart disease, heart failure, or stroke are the most common cause of death worldwide and are regularly based on risk factors like diabetes mellitus, hypertension, or obesity. At the same time, both diseases and risk factors are significantly influenced by sex hormones. In order to better understand this influence and also specifically improve the therapy of female patients, medical research has recently focused increasingly on gender-specific differences. The goal is to develop personalized, gender-specific therapy concepts for these diseases to further enhance health outcomes. The enzyme adenosine monophosphate-activated protein kinase (AMPK) is a central regulator of energy metabolism, protecting the cardiovascular system from energy depletion, thereby promoting vascular health and preventing cellular damage. AMPK confers cardioprotective effects by preventing endothelial and vascular dysfunction, and by controlling or regulating oxidative stress and inflammatory processes. For AMPK, sex-specific effects were reported, influencing metabolic and cardiovascular responses. Exercise and metabolic stress generally cause higher AMPK activity in males. At the same time, females exhibit protective mechanisms against insulin resistance or oxidative stress, particularly in conditions like obesity. Additionally, males subject to AMPK deficiency seem to experience greater cardiac and mitochondrial dysfunction. In contrast, females show improvement in cardiovascular function after pharmacological AMPK activation. These differences, influenced by hormones, body composition, and gene expression, highlight the potential to develop personalized, sex-specific AMPK-targeted therapeutic strategies for cardiovascular diseases in the future. Here, we discuss the most actual scientific background, focusing on the protective, gender-specific effects of AMPK, and highlight potential clinical applications.https://www.mdpi.com/2076-3921/14/5/615AMPKsex-specific differencesoxidative stressantioxidantcardiovascular diseases
spellingShingle Lea Strohm
Dominika Mihalikova
Alexander Czarnowski
Zita Schwaibold
Andreas Daiber
Paul Stamm
Sex-Specific Antioxidant and Anti-Inflammatory Protective Effects of AMPK in Cardiovascular Diseases
Antioxidants
AMPK
sex-specific differences
oxidative stress
antioxidant
cardiovascular diseases
title Sex-Specific Antioxidant and Anti-Inflammatory Protective Effects of AMPK in Cardiovascular Diseases
title_full Sex-Specific Antioxidant and Anti-Inflammatory Protective Effects of AMPK in Cardiovascular Diseases
title_fullStr Sex-Specific Antioxidant and Anti-Inflammatory Protective Effects of AMPK in Cardiovascular Diseases
title_full_unstemmed Sex-Specific Antioxidant and Anti-Inflammatory Protective Effects of AMPK in Cardiovascular Diseases
title_short Sex-Specific Antioxidant and Anti-Inflammatory Protective Effects of AMPK in Cardiovascular Diseases
title_sort sex specific antioxidant and anti inflammatory protective effects of ampk in cardiovascular diseases
topic AMPK
sex-specific differences
oxidative stress
antioxidant
cardiovascular diseases
url https://www.mdpi.com/2076-3921/14/5/615
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