Linked Life Data

11375257

Source:http://linkedlifedata.com/resource/pubmed/id/11375257

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-5-25
pubmed:abstractText
Recent studies have reported that hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have vasculoprotective effects independent of their lipid-lowering properties, including anti-inflammatory actions. We used intravital microscopy of the rat mesenteric microvasculature to examine the effects of rosuvastatin, a new HMG-CoA reductase inhibitor, on leukocyte-endothelium interactions induced by thrombin. Intraperitoneal administration of 0.5 and 1.25 mg kg(-1) rosuvastatin 18 h prior to the study, significantly and dose-dependently attenuated leukocyte rolling, adherence, and transmigration in the rat mesenteric microvasculature superfused with 0.5 u ml(-1) thrombin. This protective effect of rosuvastatin was reversed by intraperitoneal injection of 25 mg kg(-1) mevalonic acid 18 h before the study. Immunohistochemical detection of the endothelial cell adhesion molecule P-selectin showed a 70% decrease in endothelial cell surface expression of P-selectin in thrombin-stimulated rats given 1.25 mg kg(-1) rosuvastatin. In addition, rosuvastatin enhanced release of nitric oxide (NO) from the vascular endothelium as measured directly in rat aortic segments. Moreover, rosuvastatin failed to attenuate leukocyte-endothelium interactions in peri-intestinal venules of eNOS(-/-) mice. These data indicate that rosuvastatin exerts important anti-inflammatory effects via inhibition of endothelial cell adhesion molecule expression, and that this protective action of rosuvastatin requires release of nitric oxide by the vascular endothelium. These data also demonstrate that the mechanism of the non-lipid lowering actions of HMG-CoA reductase inhibitors in vivo may be due to reduced formation or availability of mevalonic acid within endothelial cells.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-10402448, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-10591666, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-11009552, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-1675786, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-1704376, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-1711528, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-3322462, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-6708823, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-7523213, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-7524346, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-7566020, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-7830728, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-7830734, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-7968073, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-8494355, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-8620597, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-8801446, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-8872645, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-9024134, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-9275235, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-9368582, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-9537338, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-9671773, http://linkedlifedata.com/resource/pubmed/commentcorrection/11375257-9727051
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0007-1188
pubmed:author
pubmed:issnType
Print
pubmed:volume
133
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
406-12
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:11375257-Animals, pubmed-meshheading:11375257-Anti-Inflammatory Agents, pubmed-meshheading:11375257-Aorta, pubmed-meshheading:11375257-Cell Adhesion, pubmed-meshheading:11375257-Chemotaxis, Leukocyte, pubmed-meshheading:11375257-Endothelium, Vascular, pubmed-meshheading:11375257-Fluorobenzenes, pubmed-meshheading:11375257-Gene Deletion, pubmed-meshheading:11375257-Hydroxymethylglutaryl-CoA Reductase Inhibitors, pubmed-meshheading:11375257-Ileum, pubmed-meshheading:11375257-Leukocytes, pubmed-meshheading:11375257-Male, pubmed-meshheading:11375257-Mevalonic Acid, pubmed-meshheading:11375257-Mice, pubmed-meshheading:11375257-Mice, Inbred C57BL, pubmed-meshheading:11375257-Mice, Knockout, pubmed-meshheading:11375257-Microcirculation, pubmed-meshheading:11375257-Nitric Oxide, pubmed-meshheading:11375257-Nitric Oxide Synthase, pubmed-meshheading:11375257-P-Selectin, pubmed-meshheading:11375257-Pyrimidines, pubmed-meshheading:11375257-Rats, pubmed-meshheading:11375257-Rats, Sprague-Dawley, pubmed-meshheading:11375257-Splanchnic Circulation, pubmed-meshheading:11375257-Sulfonamides, pubmed-meshheading:11375257-Thrombin
pubmed:year
2001
pubmed:articleTitle
A new HMG-CoA reductase inhibitor, rosuvastatin, exerts anti-inflammatory effects on the microvascular endothelium: the role of mevalonic acid.
pubmed:affiliation
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, PA, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't