Linked Life Data

17823371

Source:http://linkedlifedata.com/resource/pubmed/id/17823371

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-10-30
pubmed:abstractText
Deficient angiogenesis after ischemia may contribute to worse outcomes of peripheral arterial disease in patients with diabetes mellitus (DM). Vascular endothelial growth factor (VEGF) and its receptors promote angiogenesis. We hypothesized that in peripheral arterial disease, maladaptive changes in VEGF ligand/receptor expression could account for impaired angiogenesis in DM. Skeletal muscle from diet-induced, type 2 diabetic (DM) and age-matched normal chow (NC)-fed mice was collected at baseline and 3 and 10 days after hindlimb ischemia and analyzed for expression of VEGF (n=10 per group), full-length VEGF receptor (VEGFR)-1, soluble VEGFR-1, and markers of downstream VEGF signaling (n=20 per group) using ELISA, reverse transcriptase-polymerase chain reaction, and Western blots. In the absence of ischemia, DM mice had increased VEGF (NC versus DM: 26.6+/-2.6 versus 53.5+/-8.8 pg/mg protein; P<0.05), decreased soluble and membrane-bound VEGFR-1 (NC versus DM: 1.44+/-0.30 versus 0.85+/-0.08 and 1.03+/-0.10 versus 0.72+/-0.10, respectively; P<0.05), decreased phospho-AKT/AKT and phospho-endothelial NO synthase/endothelial NO synthase (NC versus DM: 0.76+/-0.2 versus 0.38+/-0.1 and 0.36+/-0.06 versus 0.25+/-0.04, respectively; P<0.05), and no change in VEGFR-2. After ischemia, both DM and NC had comparable increases in VEGF-A. VEGFR-1 and soluble VEGFR-1 expression increased in both groups, but the fold increase was significantly greater in DM. These data demonstrate that soluble VEGFR-1, an angiogenesis inhibitor, is regulated in skeletal muscle by type 2 DM and ischemia. In the absence of ischemia, despite reductions in both soluble VEGFR-1 and VEGFR-1, VEGF ligand signaling is lower in DM compared with controls. After ischemia, maladaptive upregulation of these receptors further reduces the capacity of VEGF to induce an angiogenic response, which may provide a novel target for therapy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
948-56
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17823371-Animals, pubmed-meshheading:17823371-Diabetes Mellitus, Type 2, pubmed-meshheading:17823371-Diabetic Angiopathies, pubmed-meshheading:17823371-Disease Models, Animal, pubmed-meshheading:17823371-Gene Expression, pubmed-meshheading:17823371-Hindlimb, pubmed-meshheading:17823371-Ischemia, pubmed-meshheading:17823371-Male, pubmed-meshheading:17823371-Mice, pubmed-meshheading:17823371-Mice, Inbred C57BL, pubmed-meshheading:17823371-Neovascularization, Pathologic, pubmed-meshheading:17823371-Nitric Oxide, pubmed-meshheading:17823371-RNA, Messenger, pubmed-meshheading:17823371-Regional Blood Flow, pubmed-meshheading:17823371-Signal Transduction, pubmed-meshheading:17823371-Solubility, pubmed-meshheading:17823371-Up-Regulation, pubmed-meshheading:17823371-Vascular Endothelial Growth Factor A, pubmed-meshheading:17823371-Vascular Endothelial Growth Factor Receptor-1
pubmed:year
2007
pubmed:articleTitle
Impaired angiogenesis after hindlimb ischemia in type 2 diabetes mellitus: differential regulation of vascular endothelial growth factor receptor 1 and soluble vascular endothelial growth factor receptor 1.
pubmed:affiliation
Division of Cardiology, Duke University and Durham VA Medical Center, Durham, NC 27710, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural