TY - JOUR
T1 - Transcription factors, transcriptional coregulators, and epigenetic modulation in the control of pulmonary vascular cell phenotype
T2 - Therapeutic implications for pulmonary hypertension (2015 grover conference series)
AU - Pullamsetti, Soni S.
AU - Perros, Frédéric
AU - Chelladurai, Prakash
AU - Yuan, Jason
AU - Stenmark, Kurt
N1 - Publisher Copyright:
© 2016 by the Pulmonary Vascular Research Institute. All rights reserved.
PY - 1996/12/1
Y1 - 1996/12/1
N2 - 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.
AB - 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.
KW - Epigenetics
KW - Epigenetics/transcription factor–based therapies
KW - Histone deacetylases
KW - Pulmonary arterial hypertension
KW - Transcription factors
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U2 - 10.1086/688908
DO - 10.1086/688908
M3 - Review article
AN - SCOPUS:85030551666
VL - 6
SP - 448
EP - 464
JO - Pulmonary Circulation
JF - Pulmonary Circulation
SN - 2045-8932
IS - 4
ER -