Abstract:
BACKGROUND:Cardiac mesenchymal cell (CMC) administration improves cardiac function in animal models of heart failure. Although the precise mechanisms remain unclear, transdifferentiation and paracrine signaling are suggested to underlie their cardiac reparative effects. We have shown that histone deacetylase 1 (HDAC1) inhibition enhances CMC cardiomyogenic lineage commitment. Here, we investigated the impact of HDAC1 on CMC cytokine secretion and associated paracrine-mediated activities on endothelial cell function. METHODS AND RESULTS:CMCs were transduced with shRNA constructs targeting HDAC1 (shHDAC1) or nontarget (shNT) control. Cytokine arrays were used to assess the expression of secreted proteins in conditioned medium (CM) from shHDAC1 or shNT-transduced CMCs. In vitro functional assays for cell proliferation, protection from oxidative stress, cell migration, and tube formation were performed on human endothelial cells incubated with CM from the various treatment conditions. CM from shHDAC1-transduced CMCs contained more cytokines involved in cell growth/differentiation and more efficiently promoted endothelial cell proliferation and tube formation compared with CM from shNT. After evaluating key cytokines previously implicated in cell-therapy-mediated cardiac repair, we found that basic fibroblast growth factor was significantly upregulated in shHDAC1-transduced CMCs. Furthermore, shRNA-mediated knockdown of basic fibroblast growth factor in HDAC1-depleted CMCs inhibited the effects of shHDAC1 CM in promoting endothelial proliferation and tube formation-indicating that HDAC1 depletion activates CMC proangiogenic paracrine signaling in a basic fibroblast growth factor-dependent manner. CONCLUSIONS:These results reveal a hitherto unknown role for HDAC1 in the modulation of CMC cytokine secretion and implicate the targeted inhibition of HDAC1 in CMCs as a means to enhance paracrine-mediated neovascularization in cardiac cell therapy applications.
journal_name
J Am Heart Assocjournal_title
Journal of the American Heart Associationauthors
Moore JB 4th,Zhao J,Fischer AG,Keith MCL,Hagan D,Wysoczynski M,Bolli Rdoi
10.1161/JAHA.117.006183subject
Has Abstractpub_date
2017-07-05 00:00:00issue
7issn
2047-9980pii
JAHA.117.006183journal_volume
6pub_type
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
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更新日期:2017-05-09 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.115.002290
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
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abstract:BACKGROUND:Regression of left ventricular (LV) hypertrophy (LVH) has been a goal in clinical trials. This study tests the external validity of results of clinical trials on LVH regression using a large registry from a tertiary care center, to identify phenotypes less likely to achieve regression of LVH. METHODS AND RE...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.004152
更新日期:2017-03-08 00:00:00
abstract:BACKGROUND:Renal denervation has no validated marker of procedural success. We hypothesized that successful renal denervation would reduce renal sympathetic nerve signaling demonstrated by attenuation of α-1-adrenoceptor-mediated autotransfusion during the Valsalva maneuver. METHODS AND RESULTS:In this substudy of the...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2018-06-12 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.119.012301
更新日期:2019-10-01 00:00:00
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pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2017-12-02 00:00:00
abstract:BACKGROUND:Impacts of a single radiofrequency ablation (RFA) on quality of life (QoL) were not well investigated in atrial fibrillation (AF) patients with low stroke risk. METHODS AND RESULTS:Nine hundred AF patients with low CHADS2 score (ie, CHADS2 ≤1) who completed both a baseline and 6-month Atrial Fibrillation Ef...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.115.002130
更新日期:2015-09-16 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.007442
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章,meta分析,评审
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更新日期:2016-01-25 00:00:00
abstract:BACKGROUND:Short-term exposures to fine (<2.5 μm aerodynamic diameter) ambient particulate-matter (PM) have been related with increased blood pressure (BP) in controlled-human exposure and community-based studies. However, whether coarse (2.5 to 10 μm) PM exposure increases BP is uncertain. Recent observational studies...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,随机对照试验
doi:10.1161/JAHA.113.000212
更新日期:2013-06-19 00:00:00
abstract::Background Mobile health (mHealth) technologies can deliver interventions to prevent and manage cardiovascular disease (CVD), but mHealth uptake among those with or at risk for CVD remains incompletely explored. Therefore, in this group, we assessed the prevalence of mHealth access and usage, and the association betwe...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.014390
更新日期:2019-12-17 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.006050
更新日期:2017-08-05 00:00:00
abstract:BACKGROUND:A cohort study found that 9/11-related environmental exposures and posttraumatic stress disorder increased self-reported cardiovascular disease risk. We attempted to replicate these findings using objectively defined cardiovascular disease hospitalizations in the same cohort. METHODS AND RESULTS:Data for ad...
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pub_type: 杂志文章
doi:10.1161/JAHA.113.000431
更新日期:2013-10-24 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章,随机对照试验
doi:10.1161/JAHA.119.013170
更新日期:2019-10-15 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.116.003890
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.007971
更新日期:2018-01-29 00:00:00
abstract:BACKGROUND:Psychosocial characteristics have a strong effect on risk of depression, and their direct treatment with behavioral interventions reduces rates of depression. Because new-onset poststroke depression (NPSD) is frequent, devastating, and often treatment-resistant, novel preventive efforts are needed. As a firs...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.116.003828
更新日期:2017-02-01 00:00:00
abstract::See Article Shah et al. ...
journal_title:Journal of the American Heart Association
pub_type: 评论,社论
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更新日期:2019-06-04 00:00:00
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pub_type: 杂志文章
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更新日期:2014-10-20 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
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更新日期:2019-04-02 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.015616
更新日期:2020-06-16 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.013296
更新日期:2019-11-05 00:00:00
abstract:BACKGROUND:Although statins reduce cardiovascular events, residual risk remains. Therefore, additional modalities are needed to reduce risk. We evaluated the effect of eicosapentaenoic acid and docosahexaenoic acid in pharmacologic doses added to statin treatment on coronary artery plaque volume. METHODS AND RESULTS:A...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,随机对照试验
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更新日期:2017-12-15 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.114.001407
更新日期:2014-12-11 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2017-11-29 00:00:00
abstract:BACKGROUND:The optimal timing to administer non-vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.007034
更新日期:2017-11-29 00:00:00
abstract:BACKGROUND:Ischemic stroke is a major cause of death and disability in the world. A major ischemic stroke subtype, large-vessel ischemic stroke (large artery atherosclerosis; LAA), has been shown to have some genetic components in individuals of European ancestry. However, it is not clear whether the genetic predisposi...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.115.003003
更新日期:2016-03-29 00:00:00