Linked Life Data

9073558

Source:http://linkedlifedata.com/resource/pubmed/id/9073558

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1997-5-1
pubmed:abstractText
Although clinical and experimental studies have supported a role of calcium in atherogenesis, the nature of this relationship has not been determined. The following investigation was performed to examine the effect of transmembrane calcium flux on the oxidative modification of low-density lipoprotein (LDL) by arterial smooth muscle cells (SMC). Confluent SMC were incubated in basal medium alone or in medium containing either nifedipine (0.25 microM), a calcium channel blocker, or dantrolene (10 microM), a blocker of calcium release from the endoplasmic reticulum. Cells were then suspended in medium with either physiologic (1.25 mM) or supraphysiologic (2.5 mM) calcium concentrations ([Ca2+]e) and were exposed to oxidized LDL (20 micrograms/protein/ml; 4.96 +/- 0.76 nmole malondialdehyde/mg LDL protein). Changes in cytosolic calcium ([Ca2+]i) were measured by spectrofluorometric analysis using a Fura 2-AM indicator. In similar studies, the cellular oxidation of native LDL was determined by fluorometric measurement of thiobarbituric acid-reactive substances in the media. Nifedipine and, to a lesser extent, dantrolene lowered steady-state [Ca2+]i at supraphysiologic [Ca2+]e (2.5 mM; P < 0.0002). Exposure of SMC to Ox-LDL increased [Ca2+]i (P < 10(7), which was further augmented by increasing [Ca2+]e (P < 10(-7). Nifedipine significantly reduced the calcium response to Ox-LDL proportionate to [Ca2+]e (P < 0.0002). A similar reduction in [Ca2+]i vs control was seen with dantrolene, but was independent of [Ca2+]e. TBARS assays revealed a significantly greater degree of cellular oxidation of native LDL following preincubation of SMC with Ox-LDL (P < 10(8). This effect was markedly inhibited by both nifedipine (P < 10(-8) and dantrolene (P < 10(-8), which showed some degree of synergism. These results indicate that the increase in cytosolic calcium in SMC exposed to Ox-LDL may occur through both membrane channels and reticular release. Inhibition of transmembrane calcium flux severely limits the cellular oxidation of low-density lipoprotein. These alternate means of calcium signal generation may allow a more varied response of the SMC to atherogenic stimuli and provide an opportunity for specific therapeutic intervention.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-4804
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
126-31
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Transmembrane calcium flux regulates LDL oxidation by arterial smooth muscle cells.
pubmed:affiliation
Case Western Reserve University, MetroHealth Medical Center, Cleveland, Ohio 44109, USA.
pubmed:publicationType
Journal Article