Chronic hypoxia aggravates monocrotaline-induced pulmonary arterial hypertension: a rodent relevant model to the human severe form of the disease

International audienc

Mitochondria: Roles in pulmonary hypertension

International audienc

Expression and role of connexin-based gap junctions in pulmonary inflammatory diseases

International audienc

Effects of the nerve growth factor and its carrier protein on the inflammatory response from human monocytes

International audienceBackground: The nerve growth factor (NGF) has been previously shown to be involved in cellular proliferation, differentiation, survival, or wound healing. This factor displays a variety of biological effects that yet remain to be explored. Previous data on cell lines show a pro-inflammatory role of NGF on monocytes.Objectives: The objective of the study was to investigate the pro-inflammatory effect of NGF, using a model of fresh human monocytes.Methods: Monocytes obtained from PBMC were exposed to NGF at various concentrations. Alternatively, monocytes were exposed to BSA, the NGF carrier protein without the NGF. Gene expression and cytokine release in the supernatant were monitored.Results: We found that NGF increased the expression of pro-inflammatory, chemotactic, and remodeling genes such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and C-X-C motif ligand (CXCL)8. The protein levels of CXCL8 and matrix metalloproteinase (MMP)-9 were also increased in the cell supernatants following NGF exposure. BSA alone was found to drive part of this response, bringing nuance to the inflammatory potential of the NGF.Conclusion: These data suggest that NGF is able to enhance monocyte inflammatory responses once cells are stimulated with another signal but is possibly not able to directly activate it. This could have implications for example in patients with bacterial infections, where NGF could worsen the local inflammation by over-activating immune cells

Role of Nerve Growth Factor in Development and Persistence of Experimental Pulmonary Hypertension

International audienc

Reactive oxygen species as therapeutic targets in pulmonary hypertension

International audienc

CT evaluation of small pulmonary vessels area in patients with COPD with severe pulmonary hypertension

International audienceRationale Severe pulmonary hypertension (PH) is very uncommon in COPD, and a distinct phenotype has been hypothesised. We aimed to evaluate whether CT can help to recognise this condition non-invasively by measuring small pulmonary vessels.Material and methods Patients with COPD who underwent pulmonary function tests, unenhanced CT of the chest and right heart catheterisation (RHC) during a period of stability were included in the study. From 105 included patients, 20 patients with COPD with severe PH (mean pulmonary arterial pressure, mPAP>35 mm Hg) were compared with 20 FEV1-matched and age-matched patients with COPD with mild or without PH (mPAP<35 mm Hg). The percentage of total cross-sectional area of vessels less than 5 mm2 normalised by lung area (%CSA<5) and 5–10 mm2 (%CSA5–10), the mean number of cross-sectioned vessels (CSNs) and bronchial wall thickness (WT) were measured on CT examination and compared between groups. Paw scores combining PaO2 measurement and CT parameters best correlated with mPAP were compared by receiver operating characteristic analysis to predict severe PH in COPD.Results Patients with severe PH COPD had higher %CSA and CSN values than those of patients with COPD without severe PH. Using multiple regression analysis, %CSA<5 and WT were the best predictors of mPAP in patients with and without severe PH, respectively. A score combining %CSA<5, PaO2 and WT best predicted severe PH in patients with COPD.Conclusions CT measurements of small vessels support a distinct vessel-related phenotype in patients with COPD with severe PH, and combined with WT and PaO2 parameters in the paw score, which may offer a non-invasive tool to select patients for RHC