Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-5-30
pubmed:abstractText
Angiogenesis requires the mobilization of progenitor cells from the bone marrow and homing of progenitor cells to ischemic tissue. Statins facilitate the former, and the chemokine stromal cell-derived factor-1 (SDF-1) enhances the latter. Their combined influence on angiogenesis was studied in vivo in the ischemic hindlimb C57BL/6 mouse model. The ischemic to non-ischemic perfusion ratio increased from 0.29 +/- 0.02 immediately after femoral excision to 0.51 +/- 0.10 three weeks after the surgery in the mice treated with either fluvastatin or SDF-1 alone, which is significantly better than the control (0.38 +/- 0.05, p < .05, n = 6). The combined use of fluvastatin and SDF-1 further improved the reperfusion ratio (0.62 +/- 0.08, p < .05). More cell proliferation, less apoptosis, enhanced bone marrow-derived endothelial progenitor cell (EPC) incorporation and higher capillary density were observed in ischemic tissue treated with both statin and SDF-1. In vitro mono-treatment with either fluvastatin (100 nM) or SDF-1 (100 ng/ml) facilitated EPC proliferation and migration, inhibited EPC apoptosis, enhanced expression of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9), and increased Akt phosphorylation and nitric oxide production. These effects were significantly augmented by the two agents together and ablated by inhibitors of either Akt or nitric oxide synthase (NOS). In conclusion, statin and SDF-1 additively enhance progenitor cell migration and proliferation and down-regulate EPC apoptosis, resulting in improved reperfusion via activation of the Akt/NOS pathway and up-regulation of MMP-2 and MMP-9 expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1549-4918
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1376-84
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18308946-Animals, pubmed-meshheading:18308946-Apoptosis, pubmed-meshheading:18308946-Capillaries, pubmed-meshheading:18308946-Cell Movement, pubmed-meshheading:18308946-Cell Proliferation, pubmed-meshheading:18308946-Chemokine CXCL12, pubmed-meshheading:18308946-Endothelial Cells, pubmed-meshheading:18308946-Fatty Acids, Monounsaturated, pubmed-meshheading:18308946-Hindlimb, pubmed-meshheading:18308946-Hydroxymethylglutaryl-CoA Reductase Inhibitors, pubmed-meshheading:18308946-Indoles, pubmed-meshheading:18308946-Ischemia, pubmed-meshheading:18308946-Male, pubmed-meshheading:18308946-Matrix Metalloproteinase 2, pubmed-meshheading:18308946-Matrix Metalloproteinase 9, pubmed-meshheading:18308946-Mice, pubmed-meshheading:18308946-Mice, Inbred C57BL, pubmed-meshheading:18308946-Muscles, pubmed-meshheading:18308946-NIH 3T3 Cells, pubmed-meshheading:18308946-Neovascularization, Physiologic, pubmed-meshheading:18308946-Nitric Oxide, pubmed-meshheading:18308946-Phosphorylation, pubmed-meshheading:18308946-Proto-Oncogene Proteins c-akt, pubmed-meshheading:18308946-Reperfusion Injury, pubmed-meshheading:18308946-Stem Cells
pubmed:year
2008
pubmed:articleTitle
Statin and stromal cell-derived factor-1 additively promote angiogenesis by enhancement of progenitor cells incorporation into new vessels.
pubmed:affiliation
Department of Surgery, Vascular Biology Institute, University of Miami, Miller School of Medicine, Miami, Florida, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural