Abstract:
AIMS:Caveolae are membrane microdomains where important signalling pathways are assembled and molecular effects transduced. In this study, we hypothesized that shear stress-mediated vasodilation (SSD) of mouse small coronary arteries (MCA) is caveolae-dependent. METHODS AND RESULTS:MCA (80-150 μm) isolated from wild-type (WT) and caveolin-1 null (Cav-1(-/-)) mice were subjected to physiological levels of shear stress (1-25 dynes/cm(2)) with and without pre-incubation of inhibitors of nitric oxide synthase (L-NAME), cyclooxygenase (indomethacin, INDO), or cytochrome P450 epoxygenase (SKF 525A). SSD was endothelium-dependent in WT and Cav-1(-/-) coronaries but that in Cav-1(-/-) was significantly diminished compared with WT. Pre-incubation with L-NAME, INDO, or SKF 525A significantly reduced SSD in WT but not in Cav-1(-/-) mice. Vessels from the soluble epoxide hydrolase null (Ephx2(-/-)) mice showed enhanced SSD, which was further augmented by the presence of arachidonic acid. In donor-detector-coupled vessel experiments, Cav-1(-/-) donor vessels produced diminished dilation in WT endothelium-denuded detector vessels compared with WT donor vessels. Shear stress elicited a robust intracellular Ca(2+) increase in vascular endothelial cells isolated from WT but not those from Cav-1(-/-) mice. CONCLUSION:Integrity of caveolae is critical for endothelium-dependent SSD in MCA. Cav-1(-/-) endothelium is deficient in shear stress-mediated generation of vasodilators including NO, prostaglandins, and epoxyeicosatrienoic acids. Caveolae plays a critical role in endothelial signal transduction from shear stress to vasodilator production and release.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Chai Q,Wang XL,Zeldin DC,Lee HCdoi
10.1093/cvr/cvt157subject
Has Abstractpub_date
2013-10-01 00:00:00pages
151-9issue
1eissn
0008-6363issn
1755-3245pii
cvt157journal_volume
100pub_type
杂志文章abstract:AIMS:Sphingosine-1-phosphate (S1P), a key regulator of vascular homeostasis and angiogenesis, promotes endothelial cell migration via stimulation of phosphoinositide 3-kinase (PI3K). The aim of this study was to identify the role of PI3Kbeta and gamma isoforms and their downstream effector pathways in mediating endothe...
journal_title:Cardiovascular research
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doi:10.1093/cvr/cvn159
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journal_title:Cardiovascular research
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journal_title:Cardiovascular research
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journal_title:Cardiovascular research
pub_type: 杂志文章,评审
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journal_title:Cardiovascular research
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journal_title:Cardiovascular research
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pub_type: 临床试验,杂志文章,随机对照试验
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doi:10.1093/cvr/cvw195
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pub_type: 杂志文章,评审
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更新日期:2005-07-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章,评审
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更新日期:2004-04-01 00:00:00
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doi:10.1016/j.cardiores.2005.07.010
更新日期:2006-01-01 00:00:00
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更新日期:1986-01-01 00:00:00
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更新日期:2003-09-01 00:00:00
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更新日期:1993-02-01 00:00:00
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doi:10.1093/cvr/28.3.312
更新日期:1994-03-01 00:00:00
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doi:10.1093/cvr/cvq411
更新日期:2011-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:1979-06-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章,评审
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更新日期:1997-04-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.6.990
更新日期:1993-06-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
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更新日期:2017-09-01 00:00:00