Abstract：
:Increasing evidences support that PGC-1α participates in regulating endothelial homeostasis, in part by mediating endothelial nitric oxide (NO) synthase (eNOS) activity and NO production. However, the molecular mechanisms by which PGC-1α regulates eNOS activity are not completely understood. In the present study, we investigated the effects of PGC-1α on eNOS dysfunction and further explore the underlying mechanisms. The results showed that PGC-1α expression was downregulated after AngiotensinII (AngII) treatment and paralleled with the decreased NO generation in human aortic endothelial cells. Overexpression of PGC-1α with adenovirus or pharmacological agonist ameliorated AngII-induced the decrease of NO generation, evidenced by the restoration of cGMP and nitrite concentration. Rather than affecting eNOS expression and uncoupling, PGC-1α inhibited AngII-induced decrease of eNOS serine 1177 phosphorylation through activation of PI3K/Akt signaling. In addition, PGC-1α overexpression suppressed AngII-induced the increase of PP2A-A/eNOS interaction and PP2A phosphatase activity, with a concomitant decrease in PP2A phosphorylation, leading to eNOS serine 1177 phosphorylation. However, pharmacological inhibition of PI3K/Akt signaling blunted the observed effect of PGC-1α on PP2A activity. Taken together, our findings suggest that PGC-1α overexpression improves AngII-induced eNOS dysfunction and that improved eNOS dysfunction is associated with activated PI3K/Akt pathway, impaired PP2A activity and reduced PP2A-A/eNOS association. These date indicate that forced PGC-1α expression may be a novel therapeutic approach for endothelial dysfunction.
journal_name
Vascul Pharmacoljournal_title
Vascular pharmacologyauthors
Li J,Geng XY,Cong XLdoi
10.1016/j.vph.2016.05.005subject
Has Abstractpub_date
2016-08-01 00:00:00pages
90-7eissn
1537-1891issn
1879-3649pii
S1537-1891(16)30066-0journal_volume
83pub_type
杂志文章abstract：OBJECTIVE:In patients with familial combined hyperlipidemia (FCHL), without metabolic syndrome (MS), occurrence of non-alcoholic fatty liver disease (NAFLD) is related to a specific pro-inflammatory profile, influenced by genetic traits, involved in oxidative stress and adipokine secretion. Among FCHL or MS patients, h...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2015.04.004
更新日期：2015-09-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2005.08.031
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journal_title：Vascular pharmacology
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doi：10.1016/j.vph.2005.09.006
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/s1537-1891(02)00338-5
更新日期：2003-02-01 00:00:00
abstract：:Angiogenesis has become an attractive target for the treatment of certain diseases such as cancer and rheumatoid arthritis. Our previous studies demonstrated that the saponin fraction from Gleditsia sinensis fruits had anti-angiogenic potential, and Gleditsiosides B (GB) was probably the main active constituent. In th...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2012.09.006
更新日期：2013-01-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2006.06.008
更新日期：2006-12-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2009.07.001
更新日期：2009-10-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2019.106583
更新日期：2019-01-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2006.05.006
更新日期：2006-12-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2005.01.009
更新日期：2005-02-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2005.11.006
更新日期：2006-04-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2008.11.002
更新日期：2009-03-01 00:00:00
abstract：:Angiogenesis consists in the growth of new blood vessels from pre-existing ones. Although anti-angiogenesis interventions have been shown to have therapeutic properties in human diseases such as cancer, their effect is only partial and the identification of novel modulators of angiogenesis is warranted. Recently, we r...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2011.04.001
更新日期：2011-07-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2008.02.002
更新日期：2008-04-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2005.03.002
更新日期：2005-06-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s1537-1891(02)00121-0
更新日期：2002-01-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2015.06.017
更新日期：2015-09-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2004.10.002
更新日期：2004-05-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2016.08.008
更新日期：2016-12-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2009.09.001
更新日期：2009-11-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2016.02.002
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/s1537-1891(03)00051-x
更新日期：2003-10-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/s1537-1891(02)00307-5
更新日期：2002-07-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2008.03.004
更新日期：2008-07-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2019.05.001
更新日期：2019-01-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2006.10.011
更新日期：2007-04-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2019.01.005
更新日期：2019-04-01 00:00:00
abstract：:β-Adrenoceptors (β-ARs) modulate ERK1/2 and p38 in different cells, but little is known about the contribution of these signaling pathways to the function of β-ARs in vascular tissue. Immunoblotting analysis of rat aortic rings, primary endothelial (ECs) and smooth muscle cells (SMCs) isolated from aorta showed that β...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2014.04.003
更新日期：2014-05-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2015.02.001
更新日期：2015-04-01 00:00:00
abstract：:Therapeutic modulation of angiogenesis is believed to be a prospective powerful treatment strategy to modulate the microcirculation and therefore help millions of patients with cardiovascular and cancer diseases. The often-frustrating results from late-stage clinical studies indicate an urgent need for improved assess...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2018.09.003
更新日期：2019-01-01 00:00:00
