Linked Life Data

17692319

Source:http://linkedlifedata.com/resource/pubmed/id/17692319

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-2-1
pubmed:abstractText
The enhanced production of monocytes expressing pro-inflammatory markers such as the integrin CD11b in patients with hypercholesterolemia may promote vascular inflammation and exacerbate atherogenesis. The objective of the present study was to determine whether hypercholesterolemia stimulates the production of CD11b(+) monocytes in bone marrow, and whether the renin-angiotensin system participates in this process and thus provides a target for therapeutic intervention. The dietary induction of hypercholesterolemia in adult male cynomolgus monkeys was accompanied by increased bone marrow cellularity and elevated peripheral blood and bone marrow monocyte CD11b expression. Isolated bone marrow CD34(+) hematopoietic stem cells (HSCs) evaluated by in vitro functional assays exhibited enhanced myeloproliferative capacity and differentiation into CD11b(+) monocytes. Treatment of hypercholesterolemic monkeys with the angiotensin II AT(1) receptor blocker losartan for 15 weeks reduced bone marrow cellularity, suppressed peripheral blood and bone marrow monocyte CD11b expression, and normalized CD34(+) cell function assays. All variables returned to pretreatment levels 6 weeks after discontinuation of losartan treatment. Hypercholesterolemia was associated with increased CD34(+) cell AT(1) receptor expression and an exaggerated in vitro myeloproliferative response to angiotensin II stimulation that positively correlated to plasma LDL concentrations. In vitro exposure to native low-density lipoproteins (LDL) also increased CD34(+) cell AT(1) receptor expression and the myeloproliferative response to angiotensin II stimulation in a dose-dependent and receptor-mediated manner. Our data provide support for a positive regulatory role of plasma LDL on AT(1) receptor-mediated HSC differentiation and the production of pro-atherogenic monocytes. LDL-regulated HSC function may explain in part hypercholesterolemia-induced inflammation as well as the anti-inflammatory and anti-atherosclerotic effects of AT(1) receptor blockers.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-10571970, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-10703892, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-10747353, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-10754514, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-10924095, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-11028685, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-11225655, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-11704378, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-11823761, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-11967727, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-12004086, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-12488436, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-12716819, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-12730301, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-12966515, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-14525791, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-15198742, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-16622027, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-1702327, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-17075218, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-17158350, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-2065049, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-222784, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-2590064, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-2675618, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-4086949, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-9008466, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-9350917, http://linkedlifedata.com/resource/pubmed/commentcorrection/17692319-9510370
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1879-1484
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
196
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
624-32
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Angiotensin II AT1 receptor blockade normalizes CD11b+ monocyte production in bone marrow of hypercholesterolemic monkeys.
pubmed:affiliation
Hypertension and Vascular Research Center, Wake Forest University Health Sciences, Winston-Salem, NC 27157, United States. bstrawn@wfubmc.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural