Research Information System
American Thoracic Society (ATS), United States Of America, 1 - 04 May 2012, no.517, pp.316, (Summary Text)
RATIONALE: Leptin is a neuroendocrine peptide released by adipose tissue that enhances metabolism and acts on the hypothalamus suppressing appetite. It is also involved in relevant process in the cardiovascular system and low leptin serum levels have been associated with increased mortality in humans. We hypothesized that leptin deficiency in mice will have effects the pulmonary vasculature. METHODS: We examined two groups of C57BL/6 male mice, five ob/ob (B6.VLepob/ob) leptin-deficient and five wild type (WT) (C57BL/6) control mice, aged 12 weeks. Lung tissues obtained from ob/ob and control mice were inflated and embedded in optimal cutting temperature (OCT) compound. The sections were stained with hematoxylin and eosin (H&E) for morphological examination, F4/80 for macrophages, and FSP1/S100A4 for fibroblast. Sections were also stained for collagen, hyaluronan and smooth muscle actin. Changes in pulmonary vasculature were examined in the ob/ob and compared to WT littermates by histology, immunohistochemistry and immunofluorescence staining. RESULTS: The weight was higher in ob/ob mice [weight (g), mean±SD): ob/ob 52±2.5, wildtype 30±2.5; p<0.001]. Pulmonary arterial walls were significantly thicker in the ob/ob mice when compared with wild types [The distance in pixel (median (interquartile range)): ob/ob 0.13 (0.05-0.18), wild type 0.03 (0.02-0.04); p=0.001]. There was also significant right ventricular hypertrophy in the ob/ob mice compared to controls [RV thickness (mean±SD): ob/ob 0.75±0.19, wild type; 0.58±0.13 p<0.001]. In the ob/ob mice, there was marked macrophage infiltration in pulmonary arterioles associated with increased myofibroblasts, and fibroblasts. Moreover, hyaluronan showed greater intensity in ob/ob mice compared to wild type and co-localized with SMC-actin. CONCLUSIONS: Leptin deficient mice have pathological features of pulmonary hypertension in the pulmonary vasculature that are associated with right ventricular hypertrophy.