Linked Life Data

15556945

Source:http://linkedlifedata.com/resource/pubmed/id/15556945

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-2-7
pubmed:abstractText
In the early stage of atherosclerosis, macrophages take up chemically modified low density lipoproteins (LDL) through the scavenger receptors, leading to foam cell formation in atherosclerotic lesions. To get insight into a role of the scavenger receptors in diabetes-enhanced atherosclerotic complications, the effects on class A scavenger receptor (SR-A) of high glucose exposure in vitro as well as the diabetic conditions in vivo were determined in the present study. The in vitro experiments demonstrated that high glucose exposure to human monocyte-derived macrophages led to an increased SR-A expression with a concomitant increase in the endocytic uptake of acetylated LDL and oxidized LDL. The endocytic process was significantly suppressed by an anti-SR-A neutralizing antibody. Stability analyses revealed a significant increased stability of SR-A at a mRNA level but not a protein level, indicating that high glucose-induced up-regulation of SR-A is due largely to increased stability of SR-A mRNA. High glucose-enhanced SR-A expression was prevented by protein kinase C and NAD(P)H oxidase inhibitors as well as antioxidants. High glucose-enhanced production of intracellular peroxides was visualized in these cells, which was attenuated by an antioxidant. The in vivo experiments demonstrated that peritoneal macrophages from streptozotocin-induced diabetic mice increased SR-A expression when compared with those from nondiabetic mice. Endocytic degradation of acetylated LDL and oxidized LDL were also increased with these macrophages but not with the corresponding macrophages from diabetic SR-A knock-out mice. These in vitro and in vivo results probably suggest that reactive oxygen species generated from a protein kinase C-dependent NAD(P)H oxidase pathway plays a role in the high glucose-induced up-regulation of SR-A, leading to the increased endocytic degradation of modified LDL for foam cell formation. This could be one mechanism for an increased rate of atherosclerosis in patients with diabetes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3355-64
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15556945-Animals, pubmed-meshheading:15556945-Arteriosclerosis, pubmed-meshheading:15556945-Diabetes Mellitus, Experimental, pubmed-meshheading:15556945-Diabetic Angiopathies, pubmed-meshheading:15556945-Endocytosis, pubmed-meshheading:15556945-Foam Cells, pubmed-meshheading:15556945-Gene Expression, pubmed-meshheading:15556945-Glucose, pubmed-meshheading:15556945-Humans, pubmed-meshheading:15556945-Lipoproteins, LDL, pubmed-meshheading:15556945-Macrophages, Peritoneal, pubmed-meshheading:15556945-Mice, pubmed-meshheading:15556945-Mice, Knockout, pubmed-meshheading:15556945-Monocytes, pubmed-meshheading:15556945-RNA, Messenger, pubmed-meshheading:15556945-Receptors, Immunologic, pubmed-meshheading:15556945-Receptors, Scavenger, pubmed-meshheading:15556945-Scavenger Receptors, Class A, pubmed-meshheading:15556945-Signal Transduction, pubmed-meshheading:15556945-Up-Regulation
pubmed:year
2005
pubmed:articleTitle
Expression of class A scavenger receptor is enhanced by high glucose in vitro and under diabetic conditions in vivo: one mechanism for an increased rate of atherosclerosis in diabetes.
pubmed:affiliation
Department of Medical Biochemistry, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Honjo 1-1-1, Kumamoto 860-8556, Japan.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't