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- W2213536112 abstract "In addition to its central role in metabolic homeostasis, increasing evidence suggests the neuroendocrine peptide, leptin, may represent an important mediator of cardiovascular processes including angiogenesis and endothelial nitric oxide production. Recent studies have also indicated that endothelial-derived leptin may contribute to the immunopathology in human pulmonary arterial hypertension (PAH). To investigate potential disease-specific alterations in plasma leptin levels in PAH patients and relevant animal models. Plasma levels of leptin were measured by luminex immunoassay in a cohort of stable PAH patients (57% female, 58 ± 10 yr, WHO FC 2-4, n=14) and healthy subjects (69% female, 46 ± 12 yr, n=16) were also examined. For comparison, levels were also assessed in three of the most common rodent models of PH including the rat monocrotaline (MCT, 70 mg/kg IP; male CDF, week 3 endpoint, n=10/group) and Sugen plus chronic hypoxia (SU5416, 20 mg/kg SC; male Sprague-Dawley, week 8 endpoint, n=9-12/group) models, and the mouse chronic hypoxia mouse model (Hx; male C57Bl6J, week 3 endpoint, n=9/group). All models showed significant elevations in right ventricular (RV) systolic pressure and RV hypertrophy (RV/LV+S ratio) compared to controls at the predefined experimental endpoint. Plasma leptin levels were nearly 3-fold higher in PAH patients (median 15,616 pg/mL; IQR, 5723-32390 pg/mL) versus controls (median 3,348 pg/ml; IQR, 1696-5544 pg/mL; P=0.0009), and showed potential diagnostic utility with a significant area under the corresponding receiver-operator characteristic curve (AUROC = 0.84, P=0.001). In contrast, plasma leptin levels were either reduced or unchanged in the rodent PH models. Circulating levels of leptin were significantly elevated in PAH patients, and may serve as a novel target for biomarker development. These data also suggest that current animal models of PH may fail to reproduce some of the underlying molecular changes associated with disease activity in humans." @default.
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- W2213536112 date "2015-10-01" @default.
- W2213536112 modified "2023-09-22" @default.
- W2213536112 title "ELEVATED PLASMA LEPTIN LEVELS IN PULMONARY ARTERIAL HYPERTENSION: POSSIBLE UTILITY AS A NOVEL BIOMARKER OF DISEASE ACTIVITY" @default.
- W2213536112 doi "https://doi.org/10.1016/j.cjca.2015.07.096" @default.
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