Mitochondrial Reactive Oxygen Species Dysregulation in Heart Failure with Preserved Ejection Fraction: A Fraction of the Whole
Heart failure with preserved ejection fraction (HFpEF) is a multifarious syndrome, accounting for over half of heart failure (HF) patients receiving clinical treatment. The prevalence of HFpEF is rapidly increasing in the coming decades as the global population ages. It is becoming clearer that HFpE...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-10-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/13/11/1330 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846154625488519168 |
|---|---|
| author | Caroline Silveira Martinez Ancheng Zheng Qingzhong Xiao |
| author_facet | Caroline Silveira Martinez Ancheng Zheng Qingzhong Xiao |
| author_sort | Caroline Silveira Martinez |
| collection | DOAJ |
| description | Heart failure with preserved ejection fraction (HFpEF) is a multifarious syndrome, accounting for over half of heart failure (HF) patients receiving clinical treatment. The prevalence of HFpEF is rapidly increasing in the coming decades as the global population ages. It is becoming clearer that HFpEF has a lot of different causes, which makes it challenging to find effective treatments. Currently, there are no proven treatments for people with deteriorating HF or HFpEF. Although the pathophysiologic foundations of HFpEF are complex, excessive reactive oxygen species (ROS) generation and increased oxidative stress caused by mitochondrial dysfunction seem to play a critical role in the pathogenesis of HFpEF. Emerging evidence from animal models and human myocardial tissues from failed hearts shows that mitochondrial aberrations cause a marked increase in mitochondrial ROS (mtROS) production and oxidative stress. Furthermore, studies have reported that common HF medications like beta blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and mineralocorticoid receptor antagonists indirectly reduce the production of mtROS. Despite the harmful effects of ROS on cardiac remodeling, maintaining mitochondrial homeostasis and cardiac functions requires small amounts of ROS. In this review, we will provide an overview and discussion of the recent findings on mtROS production, its threshold for imbalance, and the subsequent dysfunction that leads to related cardiac and systemic phenotypes in the context of HFpEF. We will also focus on newly discovered cellular and molecular mechanisms underlying ROS dysregulation, current therapeutic options, and future perspectives for treating HFpEF by targeting mtROS and the associated signal molecules. |
| format | Article |
| id | doaj-art-734dad9af4b6441396f40adc0ac70f07 |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-734dad9af4b6441396f40adc0ac70f072024-11-26T17:46:59ZengMDPI AGAntioxidants2076-39212024-10-011311133010.3390/antiox13111330Mitochondrial Reactive Oxygen Species Dysregulation in Heart Failure with Preserved Ejection Fraction: A Fraction of the WholeCaroline Silveira Martinez0Ancheng Zheng1Qingzhong Xiao2Centre for Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UKCentre for Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UKCentre for Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UKHeart failure with preserved ejection fraction (HFpEF) is a multifarious syndrome, accounting for over half of heart failure (HF) patients receiving clinical treatment. The prevalence of HFpEF is rapidly increasing in the coming decades as the global population ages. It is becoming clearer that HFpEF has a lot of different causes, which makes it challenging to find effective treatments. Currently, there are no proven treatments for people with deteriorating HF or HFpEF. Although the pathophysiologic foundations of HFpEF are complex, excessive reactive oxygen species (ROS) generation and increased oxidative stress caused by mitochondrial dysfunction seem to play a critical role in the pathogenesis of HFpEF. Emerging evidence from animal models and human myocardial tissues from failed hearts shows that mitochondrial aberrations cause a marked increase in mitochondrial ROS (mtROS) production and oxidative stress. Furthermore, studies have reported that common HF medications like beta blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and mineralocorticoid receptor antagonists indirectly reduce the production of mtROS. Despite the harmful effects of ROS on cardiac remodeling, maintaining mitochondrial homeostasis and cardiac functions requires small amounts of ROS. In this review, we will provide an overview and discussion of the recent findings on mtROS production, its threshold for imbalance, and the subsequent dysfunction that leads to related cardiac and systemic phenotypes in the context of HFpEF. We will also focus on newly discovered cellular and molecular mechanisms underlying ROS dysregulation, current therapeutic options, and future perspectives for treating HFpEF by targeting mtROS and the associated signal molecules.https://www.mdpi.com/2076-3921/13/11/1330heart failureheart failure with preserved ejection fraction (HFpEF)cardiac diastolic dysfunctioncardiovascular diseasereactive oxygen speciesmitochondrial |
| spellingShingle | Caroline Silveira Martinez Ancheng Zheng Qingzhong Xiao Mitochondrial Reactive Oxygen Species Dysregulation in Heart Failure with Preserved Ejection Fraction: A Fraction of the Whole Antioxidants heart failure heart failure with preserved ejection fraction (HFpEF) cardiac diastolic dysfunction cardiovascular disease reactive oxygen species mitochondrial |
| title | Mitochondrial Reactive Oxygen Species Dysregulation in Heart Failure with Preserved Ejection Fraction: A Fraction of the Whole |
| title_full | Mitochondrial Reactive Oxygen Species Dysregulation in Heart Failure with Preserved Ejection Fraction: A Fraction of the Whole |
| title_fullStr | Mitochondrial Reactive Oxygen Species Dysregulation in Heart Failure with Preserved Ejection Fraction: A Fraction of the Whole |
| title_full_unstemmed | Mitochondrial Reactive Oxygen Species Dysregulation in Heart Failure with Preserved Ejection Fraction: A Fraction of the Whole |
| title_short | Mitochondrial Reactive Oxygen Species Dysregulation in Heart Failure with Preserved Ejection Fraction: A Fraction of the Whole |
| title_sort | mitochondrial reactive oxygen species dysregulation in heart failure with preserved ejection fraction a fraction of the whole |
| topic | heart failure heart failure with preserved ejection fraction (HFpEF) cardiac diastolic dysfunction cardiovascular disease reactive oxygen species mitochondrial |
| url | https://www.mdpi.com/2076-3921/13/11/1330 |
| work_keys_str_mv | AT carolinesilveiramartinez mitochondrialreactiveoxygenspeciesdysregulationinheartfailurewithpreservedejectionfractionafractionofthewhole AT anchengzheng mitochondrialreactiveoxygenspeciesdysregulationinheartfailurewithpreservedejectionfractionafractionofthewhole AT qingzhongxiao mitochondrialreactiveoxygenspeciesdysregulationinheartfailurewithpreservedejectionfractionafractionofthewhole |