Abstract:
:Pyroptosis is a pro-inflammatory form of programmed cell death, whose genesis directly depended on caspase-1 activation. Pulmonary hypertension (PH) is a disease characterized, in part, by vascular fibrosis. Up to now, there is no report on the relationship between pyroptosis and vascular fibrosis in PH. Here, we confirmed that pyroptosis had occurred in the media of pulmonary arteries in two PH rat models and hypoxic human pulmonary arterial smooth muscle cells (hPASMCs). Caspase-1 inhibition attenuated the pathogenesis of PH, as assessed by vascular remodeling, right ventricular systolic pressure, right ventricle hypertrophy and hemodynamic parameters of pulmonary vasculature. Moreover, caspase-1 inhibition suppressed pulmonary vascular fibrosis as demonstrated by Masson staining, as well as immunohistochemistry and Western blot analysis of fibrillar collagen. In addition, Programmed death-ligand 1 (PD-L1) was markedly increased in PH, which was regulated by the transcription factor STAT1. Furthermore, PD-L1 knockdown in hPASMCs repressed the onset of hypoxia-induced pyroptosis and fibrosis. Overall, these data identify a critical STAT1-dependent posttranscriptional modification that promotes PD-L1 expression in the pyroptosis of PASMCs to modulate pulmonary vascular fibrosis and accelerate the progression of PH.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Zhang M,Xin W,Yu Y,Yang X,Ma C,Zhang H,Liu Y,Zhao X,Guan X,Wang X,Zhu Ddoi
10.1016/j.yjmcc.2019.10.008subject
Has Abstractpub_date
2020-01-01 00:00:00pages
23-33eissn
0022-2828issn
1095-8584pii
S0022-2828(19)30371-2journal_volume
138pub_type
杂志文章abstract:AIMS:Ischaemic cardiovascular disease is a major cause of morbidity and mortality worldwide. Despite promising results from pre-clinical animal models, VEGF-based strategies for therapeutic angiogenesis have yet to achieve successful reperfusion of ischaemic tissues in patients. Failure to restore efficient VEGF activi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.07.001
更新日期:2017-08-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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abstract::Small antisense RNAs like miRNA and siRNA are of crucial importance in cardiac physiology, pathology and, moreover, can be applied as therapeutic agents for the treatment of cardiovascular diseases. Identification of novel strategies for miRNA/siRNA therapy requires a comprehensive understanding of the underlying mech...
journal_title:Journal of molecular and cellular cardiology
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更新日期:2016-09-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
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doi:10.1006/jmcc.2000.1220
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0436
更新日期:1997-07-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2007.01.003
更新日期:2007-04-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,随机对照试验
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更新日期:2008-08-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.07.246
更新日期:2018-08-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.03.006
更新日期:2008-07-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.09.124
更新日期:2008-12-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.12.007
更新日期:2007-03-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.06.018
更新日期:2014-10-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(91)90047-p
更新日期:1991-05-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.10.005
更新日期:2010-02-01 00:00:00
abstract::Cardiac myosin binding protein-C (cMyBP-C) has 11 immunoglobulin or fibronectin-like domains, C0 through C10, which bind sarcomeric proteins, including titin, myosin and actin. Using bacterial expressed mouse N-terminal fragments (C0 through C3) in an in vitro motility assay of myosin-generated actin movement and the ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2011.09.019
更新日期:2012-01-01 00:00:00
abstract::Phospholipase D (PLD) plays a central role in receptor-mediated breakdown of choline phospholipids and formation of phosphatidic acid (PA), an important regulator of cardiac function. However, specific mechanisms that regulate myocardial PLD activity remain largely unknown, particularly in the human heart. We hypothes...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2003.11.008
更新日期:2004-02-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(03)00134-2
更新日期:2003-07-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2017.01.007
更新日期:2017-03-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.11.017
更新日期:2019-02-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0711
更新日期:1998-07-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2011.09.007
更新日期:2012-02-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.05.004
更新日期:2010-01-01 00:00:00
abstract::Cardiac fibroblasts represent one of the most frequent cell type in the heart of rodents and humans and alterations of their phenotype have a great impact on cardiac function. Due to aging, ischemic injuries, valvular dysfunctions, hypertension and aortic stenosis, multiple signals trigger the accumulation of extracel...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2015.12.023
更新日期:2016-03-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2020.08.003
更新日期:2020-10-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1993.1077
更新日期:1993-06-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1999.1026
更新日期:1999-10-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.08.020
更新日期:2009-11-01 00:00:00
abstract::Cardiac fibrosis is a common feature of various cardiovascular diseases. Previous studies showed that acetaldehyde dehydrogenase 2 (ALDH2) deficiency exacerbated pressure overload-induced heart failure. However, the role and mechanisms of cardiac fibrosis in this process remain largely unknown. This study aimed to inv...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2019.10.006
更新日期:2019-12-01 00:00:00