Linked Life Data

12663685

Source:http://linkedlifedata.com/resource/pubmed/id/12663685

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-6-19
pubmed:abstractText
Endothelin-1 (ET-1) signaling mechanisms have been implicated in the pathogenesis of excess coronary artery disease in diabetic dyslipidemia. We hypothesized that in diabetic dyslipidemia ET-1-induced coronary smooth muscle calcium (Ca2+m) and tyrosine phosphorylation would be increased, and the lipid lowering agent, atorvastatin, would inhibit these increases. Male Yucatan miniature swine groups were treated for 20 weeks: normal low-fat fed control, high-fat/cholesterol fed (hyperlipidemic), hyperlipidemic made diabetic with alloxan (diabetic dyslipidemic), and diabetic dyslipidemic treated with atorvastatin (atorvastatin-treated). Blood glucose values were 5-fold greater in diabetic dyslipidemic and atorvastatin-treated versus control and hyperlipidemic. Total and low-density lipoprotein (LDL) plasma cholesterol in hyperlipidemic, diabetic dyslipidemic, and atorvastatin-treated were approximately 5-fold greater than control. Intravascular ultrasound detectable coronary disease and hypertriglyceridemia were only observed in diabetic dyslipidemic and were abolished by atorvastatin. In freshly isolated cells, the Ca2+m response to ET-1 in diabetic dyslipidemic was greater than in control, hyperlipidemic, and atorvastatin-treated groups. Selective ET-1 receptor antagonists showed in the control group that the ETB subtype inhibits ETA regulation of Ca2+m. There was almost a complete switch of receptor subtype regulation of Ca2+m from largely ETA in control to an increased inhibitory interaction between ETA and ETB in hyperlipidemic and diabetic dyslipidemic groups, such that neither ETA nor ETB antagonist alone could block the ET-1-induced Ca2+m response. The inhibitory interaction was attenuated in the atorvastatin-treated group. In single cells, basal and ET-1-induced tyrosine phosphorylation in diabetic dyslipidemic were more than 3- and 6-fold greater, respectively, than in control, hyperlipidemic, and atorvastatin-treated. Attenuation by atorvastatin of coronary disease and ET-1-induced Ca2+m and tyrosine phosphorylation signaling with no change in cholesterol provides strong evidence for direct actions of atorvastatin and/or triglycerides on the vascular wall.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
306
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
132-40
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:12663685-Animals, pubmed-meshheading:12663685-Anticholesteremic Agents, pubmed-meshheading:12663685-Calcium, pubmed-meshheading:12663685-Calcium Signaling, pubmed-meshheading:12663685-Coronary Artery Disease, pubmed-meshheading:12663685-Diabetes Complications, pubmed-meshheading:12663685-Diet, pubmed-meshheading:12663685-Disease Models, Animal, pubmed-meshheading:12663685-Endothelin-1, pubmed-meshheading:12663685-Endothelins, pubmed-meshheading:12663685-Heptanoic Acids, pubmed-meshheading:12663685-Hyperlipidemias, pubmed-meshheading:12663685-Male, pubmed-meshheading:12663685-Phosphorylation, pubmed-meshheading:12663685-Pyrroles, pubmed-meshheading:12663685-Receptor, Endothelin A, pubmed-meshheading:12663685-Receptors, Endothelin, pubmed-meshheading:12663685-Swine, pubmed-meshheading:12663685-Tyrosine
pubmed:year
2003
pubmed:articleTitle
Increased endothelin-induced Ca2+ signaling, tyrosine phosphorylation, and coronary artery disease in diabetic dyslipidemic Swine are prevented by atorvastatin.
pubmed:affiliation
Department of Medical Pharmacology and Physiology, MA415 Medical Sciences Building, School of Medicine, University of Missouri, Columbia, MO 65212, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't