Abstract:
:We tested the hypothesis that oxidized low-density lipoprotein (oxLDL)-induced inactivation of Akt within endothelial progenitor cells (EPCs) is mediated at the level of phosphoinositide 3-kinase (PI3K), specifically by nitrosylation of the p85 subunit of PI3K, and that this action is critical in provoking oxLDL-induced EPC apoptosis. Hypercholesterolemic ApoE null mice had a significant reduction of the phosphorylated Akt (p-Akt)/Akt ratio in EPCs, as well as a greater percentage of apoptosis in these cells than EPCs isolated from wild-type (WT) C57Bl/6 mice. EPCs were isolated from WT spleen and exposed to oxLDL in vitro. oxLDL increased O₂⁻ and H₂O₂ in these cells and induced a dose- and time-dependent reduction in the p-Akt/Akt ratio and increase in EPC apoptosis. These effects were significantly reduced by the antioxidants superoxide dismutase, L-NAME, epicatechin and FeTPPs. oxLDL also induced nitrosylation of the p85 subunit of PI3K and subsequent dissociation of the p85 and p110 subunits, an effect significantly reduced by all the antioxidant agents tested. EPC transfection with a constitutively active Akt isoform (Ad-myrAkt) significantly reduced oxLDL-induced apoptosis of WT EPCs. The present findings indicate that oxLDL disrupts the PI3K/Akt signaling pathway at the level of p85 in EPCs. This dysfunction can be reversed by ex vivo antioxidant therapy.
journal_name
J Vasc Resjournal_title
Journal of vascular researchauthors
Tie G,Yan J,Yang Y,Park BD,Messina JA,Raffai RL,Nowicki PT,Messina LMdoi
10.1159/000313879subject
Has Abstractpub_date
2010-01-01 00:00:00pages
519-30issue
6eissn
1018-1172issn
1423-0135pii
000313879journal_volume
47pub_type
杂志文章abstract::In response to stimuli, endothelial cells release arachidonic acid, a lipid precursor of various vasoactive substances. We have investigated the relationships between cytosolic Ca2+ movements and arachidonic acid release in human umbilical vein endothelial cells. Histamine, a receptor-dependent agonist, and thapsigarg...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000025647
更新日期:1999-05-01 00:00:00
abstract::Actin cytoskeleton reorganization is regulated by various actin-binding proteins. Cofilin is the principal filament-depolymerizing protein, whose activity is reduced upon phosphorylation by LIMK. Thus, LIMK and cofilin comprise a signal transduction module regulating actin turnover and myogenic tone in healthy vascula...
journal_title:Journal of vascular research
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abstract:BACKGROUND:The aim of the present study was to evaluate different signaling pathways by which exercise training would interfere in endothelial function in obesity. Therefore, we examined adipocytokine levels and their receptors in the corpus cavernosum and femoral artery from trained rats on a high-fat diet. METHODS:F...
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journal_title:Journal of vascular research
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更新日期:1999-09-01 00:00:00
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doi:10.1159/000371490
更新日期:2014-01-01 00:00:00
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doi:10.1159/000101777
更新日期:2007-01-01 00:00:00
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journal_title:Journal of vascular research
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doi:10.1159/000158987
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journal_title:Journal of vascular research
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doi:10.1159/000076126
更新日期:2004-01-01 00:00:00
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journal_title:Journal of vascular research
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更新日期:2006-01-01 00:00:00
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journal_title:Journal of vascular research
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doi:10.1159/000025753
更新日期:2000-09-01 00:00:00
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journal_title:Journal of vascular research
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更新日期:1998-03-01 00:00:00
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journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000085721
更新日期:2005-05-01 00:00:00
abstract::Endothelin-1 (ET-1), a vasoconstrictor peptide produced by endothelial and vascular smooth muscle cells (VSMC) might play a role in vascular remodelling. To investigate the proposed 'mitogenic' potential of ET-1, we examined the effects of chronic exposure of VSMC to ET-1 on cell cycle, growth/proliferation and differ...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000158994
更新日期:1993-07-01 00:00:00
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journal_title:Journal of vascular research
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doi:10.1159/000498893
更新日期:2019-01-01 00:00:00
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journal_title:Journal of vascular research
pub_type: 杂志文章
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更新日期:2019-01-01 00:00:00
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journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000255966
更新日期:2010-01-01 00:00:00
abstract::We investigated the possible interference of smooth muscle cells with monocyte response to LDL as well as with their adhesion and transmigration in a coculture of porcine endothelial and smooth muscle cells. Lysophosphatidylcholine (LPC), a component of oxidized LDL (oxLDL), stimulated the adhesion of THP-1 cells to e...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000051081
更新日期:2001-09-01 00:00:00
abstract::The mechanosensitive nonselective cation channel (NSC(MS)) is a key player in vascular myogenic contraction. The functional channel density and pressure sensitivity of NSC(MS) in vascular myocytes were compared between pulmonary and systemic arteries (coronary, mesenteric and cerebral arteries) in the rabbit. In cell-...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000093607
更新日期:2006-01-01 00:00:00
abstract::Organic nitrates act as vasodilators and have long been used for treatment of cardiovascular diseases. However, the therapeutic effect of nitrates is limited by induction of nitrate tolerance which is associated with endothelial dysfunction and enhanced vasoconstriction. Multiple mechanisms cause nitrate tolerance inc...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000065542
更新日期:2002-07-01 00:00:00
abstract::Insulin was reported to decrease Na(+)/H(+) exchange activity in murine vascular smooth muscle (VSM) tissue. In most other cells, insulin increases activity. We tested the effects of insulin on Na(+)/H(+) exchange activity in primary cultured canine VSM cells. Intracellular pH (pH(i)) was measured with 2',7'-bis(2-car...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000329587
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:We have developed an in vitro model by organ culture of rat mesenteric arteries to imitate vascular smooth muscle cell (VSMC) receptor changes in cardiovascular disease. By using this model, alteration of VSMC thromboxane A(2) (TP) receptors was studied. METHODS AND RESULTS:After organ culture of the arteri...
journal_title:Journal of vascular research
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doi:10.1159/000153247
更新日期:2009-01-01 00:00:00
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journal_title:Journal of vascular research
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更新日期:2018-01-01 00:00:00
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journal_title:Journal of vascular research
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doi:10.1159/000113600
更新日期:2008-01-01 00:00:00
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journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000070711
更新日期:2003-03-01 00:00:00
abstract::It has been well established that wall shear stress is an important determinant of endothelial cell function and gene expression as well as of its structure. There is increasing evidence that low wall shear stress, as present in artery bifurcations opposite to the flow divider where atherosclerotic lesions preferentia...
journal_title:Journal of vascular research
pub_type: 杂志文章,评审
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更新日期:2006-01-01 00:00:00
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journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000158951
更新日期:1992-09-01 00:00:00
abstract::The novel endothelial cell tyrosine kinase receptors, Tie1 and Tie2, are essential for vascular development and remodeling in the embryo but little is known regarding the regulation of their expression and their role in the maintenance and repair of the adult vascular system. We examined the expression of Tie1 and Tie...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000025655
更新日期:1999-07-01 00:00:00
abstract:PURPOSE:Exercise elicits early adaptation of coronary vessels enabling the coronary circulation to respond adequately to higher flow demands. We hypothesized that short-term daily exercise induces biomechanical and functional remodeling of the coronary resistance arteries related to pressure. METHODS:Male rats were su...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000486571
更新日期:2018-01-01 00:00:00
abstract:UNLABELLED:Nitric oxide (NO) and cyclooxygenase (COX) derived prostaglandins (PGs) are involved in vascular homeostasis. Contradictory results have been obtained in previous studies on the putative 'cross-talk' between these two pathways. Our aim was to evaluate the interaction between NO and PG release in human microv...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000074550
更新日期:2003-09-01 00:00:00
abstract:BACKGROUND/AIMS:Endothelial colony-forming cells (ECFCs) have the potential to be used in regenerative medicine. Dysfunction of ECFCs is correlated with the onset of cardiovascular disorders, especially coronary artery disease (CAD). Binding of vascular endothelial growth factor A (VEGFA) to vascular endothelial growth...
journal_title:Journal of vascular research
pub_type: 杂志文章
doi:10.1159/000449202
更新日期:2017-01-01 00:00:00