| pubmed-article:15371635 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15371635 | lifeskim:mentions | umls-concept:C0014257 | lld:lifeskim |
| pubmed-article:15371635 | lifeskim:mentions | umls-concept:C0162638 | lld:lifeskim |
| pubmed-article:15371635 | lifeskim:mentions | umls-concept:C1801960 | lld:lifeskim |
| pubmed-article:15371635 | lifeskim:mentions | umls-concept:C0162714 | lld:lifeskim |
| pubmed-article:15371635 | lifeskim:mentions | umls-concept:C0277785 | lld:lifeskim |
| pubmed-article:15371635 | lifeskim:mentions | umls-concept:C0600688 | lld:lifeskim |
| pubmed-article:15371635 | lifeskim:mentions | umls-concept:C2266986 | lld:lifeskim |
| pubmed-article:15371635 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:15371635 | lifeskim:mentions | umls-concept:C0332120 | lld:lifeskim |
| pubmed-article:15371635 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:15371635 | pubmed:dateCreated | 2004-9-16 | lld:pubmed |
| pubmed-article:15371635 | pubmed:abstractText | HIV-protease inhibitor (HIV-PI) drugs are critical for highly active antiretroviral therapy (HAART) efficacy, but several recent reports have suggested that metabolic and/or cardiovascular toxicities are associated with these drugs. Given the importance of the HIV-PI drug class and the widespread and chronic use of these agents in an expanding patient population, further understanding of this potential drug toxicity is imperative. Here, we investigated a role for direct endothelial toxicity induced by saquinavir (SAQ), the first HIV-PI drug marketed in the United States and still an important component of HAART therapies. In initial studies using isolated vascular tissues, we observed selective impairment of endothelium-dependent vasodilation with no effect on contractile responses. Subsequent studies using human endothelial cells in culture at clinically relevant concentrations (5 and 10 microM, 2-48 h) demonstrated concentration-dependent increases in cell death, mainly via apoptosis rather than necrosis (determined via Annexin-V positive membrane labeling). Live cell imaging also demonstrated increased intracellular oxidant production (as measured by DCF fluorescence), which could be abrogated by incubation with the antioxidant N-acetylcysteine (NAC). NAC also prevented SAQ- induced apoptotic cell death. These data demonstrate that SAQ has direct toxicological effects on endothelial cells, and that the toxicity apparently involves apoptotic pathway activation via reactive oxygen and/or nitrogen species. | lld:pubmed |
| pubmed-article:15371635 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15371635 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15371635 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:15371635 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15371635 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15371635 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15371635 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15371635 | pubmed:issn | 1530-7905 | lld:pubmed |
| pubmed-article:15371635 | pubmed:author | pubmed-author:HoytDale GDG | lld:pubmed |
| pubmed-article:15371635 | pubmed:author | pubmed-author:BauerJohn AJA | lld:pubmed |
| pubmed-article:15371635 | pubmed:author | pubmed-author:ChavesAlysia... | lld:pubmed |
| pubmed-article:15371635 | pubmed:author | pubmed-author:LiuCynthiaC | lld:pubmed |
| pubmed-article:15371635 | pubmed:author | pubmed-author:BaligaReshma... | lld:pubmed |
| pubmed-article:15371635 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15371635 | pubmed:volume | 4 | lld:pubmed |
| pubmed-article:15371635 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15371635 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15371635 | pubmed:pagination | 199-206 | lld:pubmed |
| pubmed-article:15371635 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:meshHeading | pubmed-meshheading:15371635... | lld:pubmed |
| pubmed-article:15371635 | pubmed:year | 2004 | lld:pubmed |
| pubmed-article:15371635 | pubmed:articleTitle | Vascular endothelial toxicity induced by HIV protease inhibitor: evidence of oxidant-related dysfunction and apoptosis. | lld:pubmed |
| pubmed-article:15371635 | pubmed:affiliation | Department of Pharmacology, College of Pharmacy, Ohio State University, Columbus, OH 43205, USA. | lld:pubmed |
| pubmed-article:15371635 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15371635 | pubmed:publicationType | In Vitro | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15371635 | lld:pubmed |
