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Analysis of [<jats:sup>3<\/jats:sup>H]thymidine incorporation showed that 5LO and 5LO-activating protein inhibitors AA-861, nordihydroguaiaretic acid (NDGA), and MK-886 all inhibited PAEC growth in a dose-dependent manner, with maximal inhibition of &gt;90% and IC<jats:sub>50<\/jats:sub>values of 3.9, 1.8, and 0.48 \u03bcM, respectively. The effect of AA-861 and NDGA correlated with their effect on 5LO activity in PAECs. Concentrations of these inhibitors at or below their IC<jats:sub>90<\/jats:sub>values did not cause significant cell death as determined by lactate dehydrogenase release, but decreased cell doubling, as measured by cell counting at 24 h after serum replenishment. Analysis of DNA content suggested that the inhibitors led to an accumulation of PAECs at the G<jats:sub>0<\/jats:sub>\/G<jats:sub>1<\/jats:sub>phase. Antisense oligonucleotides to 5LO mRNA delivered at a transfection efficiency of \u223c60% inhibited cell growth by 40 \u00b1 26% compared with that of a sequence-unrelated oligonucleotide. Indomethacin had no effect on PAEC growth over a range of concentrations (0.3\u20135 \u03bcM). These data show that 5LO inhibitors impaired the proliferative response of the cultured PAECs, suggesting that this enzyme may contribute to PAEC growth under certain pathological conditions.<\/jats:p>","DOI":"10.1152\/ajpheart.00003.2001","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:00:38Z","timestamp":1425412838000},"page":"H585-H593","source":"Crossref","is-referenced-by-count":29,"title":["5-Lipoxygenase and human pulmonary artery endothelial cell proliferation"],"prefix":"10.1152","volume":"282","author":[{"given":"Jennifer L.","family":"Walker","sequence":"first","affiliation":[{"name":"Whitaker Cardiovascular Institute and Evans Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Loscalzo","sequence":"additional","affiliation":[{"name":"Whitaker Cardiovascular Institute and Evans Department of Medicine, Boston 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