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Nitric Oxide and Asymmetric Dimethylarginine Levels in Malignancy Associated Thrombosis and Their Modulation by Anticoagulants
Author(s) -
Hoppensteadt Debra,
Jeske Walter,
Fareed Daniel,
Iqbal Omer,
Bick Rodger,
Lale Ajit,
Fareed Jawed
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1167-b
Subject(s) - asymmetric dimethylarginine , medicine , nitric oxide , cancer , endothelial dysfunction , malignancy , endocrinology , thrombosis , gastroenterology , arginine , chemistry , biochemistry , amino acid
Nitric oxide (NO) is an important endothelially derived vasoactive mediator. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase. While an association between ADMA levels and cardiovascular diseases is known, no information on ADMA levels in cancer patients is available. It was hypothesized that endothelial dysfunction in cancer patients may result in increased ADMA levels. Plasma samples were analyzed from an open‐label, multi‐dose, active comparator study in which all patients (n=110) were initially treated with enoxaparin (E; 1 to 1.5 mg/kg SC). After 5 days of treatment, half of the patients continued to receive E and the other half received warfarin (W) for up to 12 weeks. Baseline (BL), 5 days post E (IPE) and 4–6 week blood samples from the E and W treated groups were analyzed for ADMA and NO levels (Cardiovasics, Palo Alto, CA; R&D Systems, Minneapolis, MN). Relative to aged matched controls, ADMA and NO levels were markedly elevated in cancer patients. The E treated group showed a marked decrease in ADMA levels throughout the treatment period. In the W converted group, ADMA levels rebounded to an increased level. The down‐regulation of NO was similar for both E and W. These results suggest that patients with cancer and thrombosis exhibit simultaneous up‐regulation of ADMA and NO. While enoxaparin and warfarin differentially regulate ADMA, both result in down‐regulation of NO. These studies underscore the anti‐inflammatory mechanisms by which low molecular weight heparins such as E mediate their therapeutic effects in cancer associated thrombosis.