Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Attempt to read property "Count" on bool
Filename: helpers/my_audit_helper.php
Line Number: 3100
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Angiogenesis is a multistep process which is orchestrated by intercellular signaling. We developed an in vitro model of human angiogenesis to identify a pathologic angiogenesis and intercellular signaling in high glucose condition. We co-cultivated human endothelial cells (ECs) and smooth muscle cells (SMCs) in a spheroid on an SMC monolayer for 7 days either in high glucose or in control condition. We analyzed vascular growth and expression of notch or its ligands with confocal microscopy. Abnormal angiogenesis by high glucose condition was characterized by (1) increased sprouting and branching (high glucose vs. normal: number of sprouts 20.3±1.5 vs. 13.7±2.9, p=0.024; number of branching points 7.6±2.5 vs. 2.3±2.1, p=0.047), (2) decreased vascular diameter (diameter of the tubes 13.4±6. 1μm vs. 19.1±8.8 μm, p=0.012) and (3) destabilization of the tubes. We identified that high glucose induced jagged 1 and suppressed notch1 in ECs whereas it did not affect Dll4. Constitutive jagged 1 overexpression or inhibition of notch1 in ECs induced abnormal angiogenesis as the high glucose condition did. Endothelial-specific shRNA targeting jagged 1 rescued the aberrant angiogenesis in high glucose condition. High glucose condition induced an abnormal endothelial intercellular signaling leading to aberrant angiogenesis. It is a novel mechanism of diabetic microvasculopathy which can be a therapeutic target beyond glucose control.
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Source |
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http://dx.doi.org/10.1016/j.yjmcc.2013.12.006 | DOI Listing |
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