Molecular Research in Chronic Thromboembolic Pulmonary Hypertension

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a debilitating disease, for which the underlying pathophysiological mechanisms have yet to be fully elucidated. Occurrence of a pulmonary embolism (PE) is a major risk factor for the development of CTEPH, with non-resolution of the thrombus be...

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Main Authors: Isabelle Opitz, Michaela B. Kirschner
Format: Article
Language:English
Published: MDPI AG 2019-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/20/3/784
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spelling doaj-c548a2126cec44779152f4c9828d95b92020-11-25T00:30:03ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-02-0120378410.3390/ijms20030784ijms20030784Molecular Research in Chronic Thromboembolic Pulmonary HypertensionIsabelle Opitz0Michaela B. Kirschner1Department of Thoracic Surgery, University Hospital Zurich, 8091 Zurich, SwitzerlandDepartment of Thoracic Surgery, University Hospital Zurich, 8091 Zurich, SwitzerlandChronic Thromboembolic Pulmonary Hypertension (CTEPH) is a debilitating disease, for which the underlying pathophysiological mechanisms have yet to be fully elucidated. Occurrence of a pulmonary embolism (PE) is a major risk factor for the development of CTEPH, with non-resolution of the thrombus being considered the main cause of CTEPH. Polymorphisms in the α-chain of fibrinogen have been linked to resistance to fibrinolysis in CTEPH patients, and could be responsible for development and disease progression. However, it is likely that additional genetic predisposition, as well as genetic and molecular alterations occurring as a consequence of tissue remodeling in the pulmonary arteries following a persistent PE, also play an important role in CTEPH. This review summarises the current knowledge regarding genetic differences between CTEPH patients and controls (with or without pulmonary hypertension). Mutations in BMPR2, differential gene and microRNA expression, and the transcription factor FoxO1 have been suggested to be involved in the processes underlying the development of CTEPH. While these studies provide the first indications regarding important dysregulated pathways in CTEPH (e.g., TGF-β and PI3K signaling), additional in-depth investigations are required to fully understand the complex processes leading to CTEPH.https://www.mdpi.com/1422-0067/20/3/784chronic thromboembolic pulmonary hypertensionpathophysiologygenetic alterationsmolecular factorsmicroRNAsmutationsbiomarkers
collection DOAJ
language English
format Article
sources DOAJ
author Isabelle Opitz
Michaela B. Kirschner
spellingShingle Isabelle Opitz
Michaela B. Kirschner
Molecular Research in Chronic Thromboembolic Pulmonary Hypertension
International Journal of Molecular Sciences
chronic thromboembolic pulmonary hypertension
pathophysiology
genetic alterations
molecular factors
microRNAs
mutations
biomarkers
author_facet Isabelle Opitz
Michaela B. Kirschner
author_sort Isabelle Opitz
title Molecular Research in Chronic Thromboembolic Pulmonary Hypertension
title_short Molecular Research in Chronic Thromboembolic Pulmonary Hypertension
title_full Molecular Research in Chronic Thromboembolic Pulmonary Hypertension
title_fullStr Molecular Research in Chronic Thromboembolic Pulmonary Hypertension
title_full_unstemmed Molecular Research in Chronic Thromboembolic Pulmonary Hypertension
title_sort molecular research in chronic thromboembolic pulmonary hypertension
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1422-0067
publishDate 2019-02-01
description Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a debilitating disease, for which the underlying pathophysiological mechanisms have yet to be fully elucidated. Occurrence of a pulmonary embolism (PE) is a major risk factor for the development of CTEPH, with non-resolution of the thrombus being considered the main cause of CTEPH. Polymorphisms in the α-chain of fibrinogen have been linked to resistance to fibrinolysis in CTEPH patients, and could be responsible for development and disease progression. However, it is likely that additional genetic predisposition, as well as genetic and molecular alterations occurring as a consequence of tissue remodeling in the pulmonary arteries following a persistent PE, also play an important role in CTEPH. This review summarises the current knowledge regarding genetic differences between CTEPH patients and controls (with or without pulmonary hypertension). Mutations in BMPR2, differential gene and microRNA expression, and the transcription factor FoxO1 have been suggested to be involved in the processes underlying the development of CTEPH. While these studies provide the first indications regarding important dysregulated pathways in CTEPH (e.g., TGF-β and PI3K signaling), additional in-depth investigations are required to fully understand the complex processes leading to CTEPH.
topic chronic thromboembolic pulmonary hypertension
pathophysiology
genetic alterations
molecular factors
microRNAs
mutations
biomarkers
url https://www.mdpi.com/1422-0067/20/3/784
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