Linked Life Data

21464389

Source:http://linkedlifedata.com/resource/pubmed/id/21464389

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-4-21
pubmed:abstractText
The interactions between the renin-angiotensin system and neovascularization in atherosclerotic plaque development are unclear. We investigated the effects of angiotensin II type 1 receptor antagonism in the pathogenesis of atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice with a special focus on plaque neovascularization. ApoE(-/-) mice fed a high-fat diet were randomly assigned to 1 of 2 groups and administered vehicle or olmesartan for 12 weeks. Quantification of plaque areas at the aortic root and in the thoracic and abdominal aorta revealed that, in all 3 of the regions, olmesartan reduced intimal neovessel density and the mRNA levels of toll-like receptor (TLR) 2 and TLR4. Olmesartan increased the levels of collagen and elastin, reduced the level of macrophages in the aortic root, and reduced the mRNA and the activity of matrix metalloproteinase (MMP) 2 in aortic roots and thoracic aortas. Aortic ring assay revealed that olmesartan-treated ApoE(-/-) mice had a markedly lower angiogenic response than that of untreated ApoE(-/-) mice. Bone marrow-derived endothelial progenitor cell-like c-Kit(+) cells from olmesartan-treated ApoE(-/-) mice showed marked impairment of cellular functions and lower expression of TLR2/TLR4 and MMP-2 compared with those of untreated controls. MMP-2 deficiency reduced intimal neovessel density and atherosclerotic lesion formation. Olmesartan and small-interfering RNA targeting TLR2 reduced the levels of TLR2, and MMP-2 mRNA induced angiotensin II in cultured endothelial cells. Angiotensin II type 1 receptor antagonism appears to inhibit intimal neovascularization in ApoE(-/-) mice, partly by reducing TLR2/TLR4-mediated inflammatory action and MMP activation, thus decreasing atherosclerotic plaque growth and increasing plaque instability.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
981-9
pubmed:meshHeading
pubmed-meshheading:21464389-Analysis of Variance, pubmed-meshheading:21464389-Angiotensin II Type 1 Receptor Blockers, pubmed-meshheading:21464389-Animals, pubmed-meshheading:21464389-Aorta, pubmed-meshheading:21464389-Apolipoproteins E, pubmed-meshheading:21464389-Atherosclerosis, pubmed-meshheading:21464389-Dietary Fats, pubmed-meshheading:21464389-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:21464389-Imidazoles, pubmed-meshheading:21464389-Male, pubmed-meshheading:21464389-Matrix Metalloproteinase 2, pubmed-meshheading:21464389-Mice, pubmed-meshheading:21464389-Mice, Knockout, pubmed-meshheading:21464389-Neovascularization, Pathologic, pubmed-meshheading:21464389-RNA, Small Interfering, pubmed-meshheading:21464389-Random Allocation, pubmed-meshheading:21464389-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21464389-Tetrazoles, pubmed-meshheading:21464389-Toll-Like Receptor 2, pubmed-meshheading:21464389-Toll-Like Receptor 4, pubmed-meshheading:21464389-Tunica Intima
pubmed:year
2011
pubmed:articleTitle
Angiotensin type 1 receptor blocker reduces intimal neovascularization and plaque growth in apolipoprotein E-deficient mice.
pubmed:affiliation
Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Japan. chengxw0908@yahoo.com.cn
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural