Abstract：
:Arterial wall remodeling underlies increased pulmonary vascular resistance and right heart failure in pulmonary arterial hypertension (PAH). None of the established vasodilator drug therapies for PAH prevents or reverse established arterial wall thickening, stiffening, and hypercontractility. Therefore, new approaches are needed to achieve long-acting prevention and reversal of occlusive pulmonary vascular remodeling. Several promising new drug classes are emerging from a better understanding of pulmonary vascular gene expression programs. In this review, potential epigenetic targets for small molecules and oligonucleotides will be described. Most are in preclinical studies aimed at modifying the growth of vascular wall cells in vitro or normalizing vascular remodeling in PAH animal models. Initial success with lung-directed delivery of oligonucleotides targeting microRNAs suggests other epigenetic mechanisms might also be suitable drug targets. Those targets include DNA methylation, proteins of the chromatin remodeling machinery, and long noncoding RNAs, all of which act as epigenetic regulators of vascular wall structure and function. The progress in testing small molecules and oligonucleotide-based drugs in PAH models is summarized.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Gerthoffer Wdoi
10.3390/ijms21239222subject
Has Abstractpub_date
2020-12-03 00:00:00issue
23issn
1422-0067pii
ijms21239222journal_volume
21pub_type
杂志文章,评审abstract：:In vivo inoculation of cells such as tumor cells and induced pluripotent stem (iPS)/embryonic stem (ES) cells into immunocompromised mice has been considered as a powerful technique to evaluate their potential to proliferate or differentiate into various cell types originating from three germ cell layers. Subcutaneous...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
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journal_title：International journal of molecular sciences
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更新日期：2015-09-07 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
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更新日期：2018-04-09 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2018-12-17 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2018-01-24 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2020-03-25 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2013-07-04 00:00:00
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journal_title：International journal of molecular sciences
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doi：10.3390/ijms17071089
更新日期：2016-07-08 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2020-09-24 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19051426
更新日期：2018-05-10 00:00:00
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journal_title：International journal of molecular sciences
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doi：10.3390/ijms22020585
更新日期：2021-01-08 00:00:00
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journal_title：International journal of molecular sciences
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doi：10.3390/ijms21197077
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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更新日期：2019-08-09 00:00:00
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journal_title：International journal of molecular sciences
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更新日期：2020-07-28 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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更新日期：2014-10-23 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms131013605
更新日期：2012-10-22 00:00:00
