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  Transcription factors, transcriptional coregulators, and epigenetic modulation in the control of pulmonary vascular cell phenotype: therapeutic implications for pulmonary hypertension (2015 Grover Conference series)

Pullamsetti, S. S., Perros, F., Chelladurai, P., Yuan, J., & Stenmark, K. (2016). Transcription factors, transcriptional coregulators, and epigenetic modulation in the control of pulmonary vascular cell phenotype: therapeutic implications for pulmonary hypertension (2015 Grover Conference series). Pulmonary Circulation, 6(4), 448-464. doi:10.1086/688908.

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 Creators:
Pullamsetti, Soni Savai1, Author              
Perros, Frederic, Author
Chelladurai, Prakash1, Author              
Yuan, Jason, Author
Stenmark, Kurt, Author
Affiliations:
1Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591698              

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Free keywords: SMOOTH-MUSCLE-CELLS; TO-MESENCHYMAL TRANSITION; HYPOXIA-INDUCIBLE FACTOR-1; RECEPTOR TYPE-II; ARTERIAL-HYPERTENSION; UP-REGULATION; GENOME-WIDE; VENOOCCLUSIVE DISEASE; NUCLEAR-LOCALIZATION; DRIVEN PROLIFERATIONCardiovascular System & Cardiology; Respiratory System; transcription factors; epigenetics; pulmonary arterial hypertension; histone deacetylases; epigenetics/transcription factor-based therapies;
 Abstract: Pulmonary hypertension (PH) is a complex and multifactorial disease involving genetic, epigenetic, and environmental factors. Numerous stimuli and pathological conditions facilitate severe vascular remodeling in PH by activation of a complex cascade of signaling pathways involving vascular cell proliferation, differentiation, and inflammation. Multiple signaling cascades modulate the activity of certain sequence-specific DNA-binding transcription factors (TFs) and coregulators that are critical for the transcriptional regulation of gene expression that facilitates PH-associated vascular cell phenotypes, as demonstrated by several studies summarized in this review. Past studies have largely focused on the role of the genetic component in the development of PH, while the presence of epigenetic alterations such as microRNAs, DNA methylation, histone levels, and histone deacetylases in PH is now also receiving increasing attention. Epigenetic regulation of chromatin structure is also recognized to influence gene expression in development or disease states. Therefore, a complete understanding of the mechanisms involved in altered gene expression in diseased cells is vital for the design of novel therapeutic strategies. Recent technological advances in DNA sequencing will provide a comprehensive improvement in our understanding of mechanisms involved in the development of PH. This review summarizes current concepts in TF and epigenetic control of cell phenotype in pulmonary vascular disease and discusses the current issues and possibilities in employing potential epigenetic or TF-based therapies for achieving complete reversal of PH.

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Language(s): eng - English
 Dates: 2016
 Publication Status: Published in print
 Pages: 17
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000389303800005
DOI: 10.1086/688908
 Degree: -

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Title: Pulmonary Circulation
Source Genre: Journal
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Publ. Info: 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA : UNIV CHICAGO PRESS
Pages: - Volume / Issue: 6 (4) Sequence Number: - Start / End Page: 448 - 464 Identifier: ISSN: 2045-8932