Transthyretin Cardiac Amyloidosis: Pathogenesis, Treatments, and Emerging Role in Heart Failure with Preserved Ejection Fraction
Transthyretin (TTR) amyloidosis causes heart failure from cardiac deposition of TTR amyloid fibrils, the by-product of TTR homotetramer disassembly. Wild-type (WT) TTR deposition leads to senile amyloidosis, predominantly manifesting with cardiomyopathy. Missense mutations in the TTR gene result in...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2014-01-01
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| Series: | Clinical Medicine Insights: Cardiology |
| Online Access: | https://doi.org/10.4137/CMC.S15719 |
| _version_ | 1819011006228070400 |
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| author | Van-Khue Ton Monica Mukherjee Daniel P. Judge |
| author_facet | Van-Khue Ton Monica Mukherjee Daniel P. Judge |
| author_sort | Van-Khue Ton |
| collection | DOAJ |
| description | Transthyretin (TTR) amyloidosis causes heart failure from cardiac deposition of TTR amyloid fibrils, the by-product of TTR homotetramer disassembly. Wild-type (WT) TTR deposition leads to senile amyloidosis, predominantly manifesting with cardiomyopathy. Missense mutations in the TTR gene result in familial TTR amyloidosis. Certain mutations are more likely to affect the heart, while others cause more neurologic involvement. Extracellular fibril deposition triggers intracellular stress response, upregulation of the inflammatory cascades, apoptosis, and organ dysfunction. Recent studies suggest that TTR cardiac amyloid may be a significant contributor to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Summarized in this review are the molecular pathways underlying the cellular toxicity of TTR amyloid fibrils and the emerging therapies aimed at TTR tetramer stabilization, abrogation of TTR synthesis in the liver, or inhibition of amyloidogenesis. |
| first_indexed | 2024-12-21T01:21:17Z |
| format | Article |
| id | doaj.art-31c342486215446990011271426af077 |
| institution | Directory Open Access Journal |
| issn | 1179-5468 |
| language | English |
| last_indexed | 2024-12-21T01:21:17Z |
| publishDate | 2014-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Clinical Medicine Insights: Cardiology |
| spelling | doaj.art-31c342486215446990011271426af0772022-12-21T19:20:38ZengSAGE PublishingClinical Medicine Insights: Cardiology1179-54682014-01-018s110.4137/CMC.S15719Transthyretin Cardiac Amyloidosis: Pathogenesis, Treatments, and Emerging Role in Heart Failure with Preserved Ejection FractionVan-Khue Ton0Monica Mukherjee1Daniel P. Judge2Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA.Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA.Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA.Transthyretin (TTR) amyloidosis causes heart failure from cardiac deposition of TTR amyloid fibrils, the by-product of TTR homotetramer disassembly. Wild-type (WT) TTR deposition leads to senile amyloidosis, predominantly manifesting with cardiomyopathy. Missense mutations in the TTR gene result in familial TTR amyloidosis. Certain mutations are more likely to affect the heart, while others cause more neurologic involvement. Extracellular fibril deposition triggers intracellular stress response, upregulation of the inflammatory cascades, apoptosis, and organ dysfunction. Recent studies suggest that TTR cardiac amyloid may be a significant contributor to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Summarized in this review are the molecular pathways underlying the cellular toxicity of TTR amyloid fibrils and the emerging therapies aimed at TTR tetramer stabilization, abrogation of TTR synthesis in the liver, or inhibition of amyloidogenesis.https://doi.org/10.4137/CMC.S15719 |
| spellingShingle | Van-Khue Ton Monica Mukherjee Daniel P. Judge Transthyretin Cardiac Amyloidosis: Pathogenesis, Treatments, and Emerging Role in Heart Failure with Preserved Ejection Fraction Clinical Medicine Insights: Cardiology |
| title | Transthyretin Cardiac Amyloidosis: Pathogenesis, Treatments, and Emerging Role in Heart Failure with Preserved Ejection Fraction |
| title_full | Transthyretin Cardiac Amyloidosis: Pathogenesis, Treatments, and Emerging Role in Heart Failure with Preserved Ejection Fraction |
| title_fullStr | Transthyretin Cardiac Amyloidosis: Pathogenesis, Treatments, and Emerging Role in Heart Failure with Preserved Ejection Fraction |
| title_full_unstemmed | Transthyretin Cardiac Amyloidosis: Pathogenesis, Treatments, and Emerging Role in Heart Failure with Preserved Ejection Fraction |
| title_short | Transthyretin Cardiac Amyloidosis: Pathogenesis, Treatments, and Emerging Role in Heart Failure with Preserved Ejection Fraction |
| title_sort | transthyretin cardiac amyloidosis pathogenesis treatments and emerging role in heart failure with preserved ejection fraction |
| url | https://doi.org/10.4137/CMC.S15719 |
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