Targeting cardiac fibrosis in heart failure with preserved ejection fraction: mirage or miracle?
Abstract Cardiac fibrosis is central to the pathology of heart failure, particularly heart failure with preserved ejection fraction (HFpEF). Irrespective of the underlying profibrotic condition (e.g. ageing, diabetes, hypertension), maladaptive cardiac fibrosis is defined by the transformation of re...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2020-10-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201910865 |
| _version_ | 1797285186029748224 |
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| author | Mark Sweeney Ben Corden Stuart A Cook |
| author_facet | Mark Sweeney Ben Corden Stuart A Cook |
| author_sort | Mark Sweeney |
| collection | DOAJ |
| description | Abstract Cardiac fibrosis is central to the pathology of heart failure, particularly heart failure with preserved ejection fraction (HFpEF). Irrespective of the underlying profibrotic condition (e.g. ageing, diabetes, hypertension), maladaptive cardiac fibrosis is defined by the transformation of resident fibroblasts to matrix‐secreting myofibroblasts. Numerous profibrotic factors have been identified at the molecular level (e.g. TGFβ, IL11, AngII), which activate gene expression programs for myofibroblast activation. A number of existing HF therapies indirectly target fibrotic pathways; however, despite multiple clinical trials in HFpEF, a specific clinically effective antifibrotic therapy remains elusive. Therapeutic inhibition of TGFβ, the master‐regulator of fibrosis, has unfortunately proven toxic and ineffective in clinical trials to date, and new approaches are needed. In this review, we discuss the pathophysiology and clinical implications of interstitial fibrosis in HFpEF. We provide an overview of trials targeting fibrosis in HFpEF to date and discuss the promise of potential new therapeutic approaches and targets in the context of underlying molecular mechanisms. |
| first_indexed | 2024-03-07T17:59:37Z |
| format | Article |
| id | doaj.art-54858a02690040f8b0a63c266471f308 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T17:59:37Z |
| publishDate | 2020-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-54858a02690040f8b0a63c266471f3082024-03-02T11:03:56ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842020-10-011210n/an/a10.15252/emmm.201910865Targeting cardiac fibrosis in heart failure with preserved ejection fraction: mirage or miracle?Mark Sweeney0Ben Corden1Stuart A Cook2MRC‐London Institute of Medical Sciences Hammersmith Hospital Campus London UKMRC‐London Institute of Medical Sciences Hammersmith Hospital Campus London UKMRC‐London Institute of Medical Sciences Hammersmith Hospital Campus London UKAbstract Cardiac fibrosis is central to the pathology of heart failure, particularly heart failure with preserved ejection fraction (HFpEF). Irrespective of the underlying profibrotic condition (e.g. ageing, diabetes, hypertension), maladaptive cardiac fibrosis is defined by the transformation of resident fibroblasts to matrix‐secreting myofibroblasts. Numerous profibrotic factors have been identified at the molecular level (e.g. TGFβ, IL11, AngII), which activate gene expression programs for myofibroblast activation. A number of existing HF therapies indirectly target fibrotic pathways; however, despite multiple clinical trials in HFpEF, a specific clinically effective antifibrotic therapy remains elusive. Therapeutic inhibition of TGFβ, the master‐regulator of fibrosis, has unfortunately proven toxic and ineffective in clinical trials to date, and new approaches are needed. In this review, we discuss the pathophysiology and clinical implications of interstitial fibrosis in HFpEF. We provide an overview of trials targeting fibrosis in HFpEF to date and discuss the promise of potential new therapeutic approaches and targets in the context of underlying molecular mechanisms.https://doi.org/10.15252/emmm.201910865CMRfibroblastfibrosisheart failureHFpEF |
| spellingShingle | Mark Sweeney Ben Corden Stuart A Cook Targeting cardiac fibrosis in heart failure with preserved ejection fraction: mirage or miracle? EMBO Molecular Medicine CMR fibroblast fibrosis heart failure HFpEF |
| title | Targeting cardiac fibrosis in heart failure with preserved ejection fraction: mirage or miracle? |
| title_full | Targeting cardiac fibrosis in heart failure with preserved ejection fraction: mirage or miracle? |
| title_fullStr | Targeting cardiac fibrosis in heart failure with preserved ejection fraction: mirage or miracle? |
| title_full_unstemmed | Targeting cardiac fibrosis in heart failure with preserved ejection fraction: mirage or miracle? |
| title_short | Targeting cardiac fibrosis in heart failure with preserved ejection fraction: mirage or miracle? |
| title_sort | targeting cardiac fibrosis in heart failure with preserved ejection fraction mirage or miracle |
| topic | CMR fibroblast fibrosis heart failure HFpEF |
| url | https://doi.org/10.15252/emmm.201910865 |
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