Linked Life Data

9395516

Source:http://linkedlifedata.com/resource/pubmed/id/9395516

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
50
pubmed:dateCreated
1998-1-15
pubmed:abstractText
Hypoxia induces vasoconstriction, in part, by down-regulating endothelial cell nitric oxide synthase (ecNOS) expression. Previous studies indicate that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitors improve endothelium-dependent relaxation by increasing ecNOS activity. To determine whether HMG CoA reductase inhibitors can prevent hypoxia-mediated down-regulation of ecNOS function and expression, human endothelial cells were exposed to hypoxia (3% O2) in the presence of HMG CoA reductase inhibitors simvastatin and lovastatin for various durations (0-48 h). Hypoxia decreased ecNOS protein and mRNA levels in a time-dependent manner, resulting in a 4- and 9-fold reduction after 48 h, respectively. In a concentration-dependent manner, simvastatin, and to a lesser extent, lovastatin, prevented the down-regulation of ecNOS expression by hypoxia. Simvastatin-induced changes in ecNOS expression correlated with changes in endothelial NO production and were reversed by treatment with L-mevalonate. Actinomycin D studies revealed that under hypoxic conditions, simvastatin increased ecNOS mRNA half-life from 13 to 38 h. Nuclear run-on studies showed that simvastatin had no effect on repression of ecNOS gene transcription by hypoxia. These results indicate that HMG CoA reductase inhibitors regulate ecNOS function and expression through changes in ecNOS mRNA stability and suggest that treatment with HMG CoA reductase inhibitors may have beneficial effects in patients with hypoxia-mediated pulmonary hypertension.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31725-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Inhibition of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase blocks hypoxia-mediated down-regulation of endothelial nitric oxide synthase.
pubmed:affiliation
Cardiovascular Division, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't