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IL-11 increases levels and activates circulating fibrocytes in different pulmonary hypertension animal models.
In conclusion, IL-11 promotes an increase of circulating fibrocytes, their adhesion to HPAECs and phenotypic switching to myofibroblast.
Source: European Respiratory Journal - December 1, 2022 Category: Respiratory Medicine Authors: Roger, I., Milara, J., Montero, P., Belhadj, N., Cortijo, J. Tags: 13.01 - Pulmonary hypertension Source Type: research

COX2 expression is downregulated in a shear stress magnitude-dependent manner in BMPR2-silenced HPAECs: implications for prostacyclin deficiency in PAH
Conclusion: BMPR2 loss may disrupt the flow-driven production of COX2 in HPAECs, which may be an underlying mechanism of endothelial dysfunction in PAH.
Source: European Respiratory Journal - December 1, 2022 Category: Respiratory Medicine Authors: Mahomed, A., Burke-Gaffney, A., Ghazaly, M., Naser, J., Toe, Q., Quinlan, G., Wort, S. J. Tags: 13.01 - Pulmonary hypertension Source Type: research

Role of Connexin 43 increased expression in pulmonary arterial hyperreactivityinduced by the nerve growth factor NGF
In conclusion, NGF pathway is upregulated in IPAH cells. NGF increases Cx43 PA expression through activation of its TrkA receptor. NGF-induced Cx43 increased expression upregulates GAP junction activity, thus promoting PA hyperreactivity.
Source: European Respiratory Journal - November 25, 2021 Category: Respiratory Medicine Authors: Cardouat, g., Douard, M., Roubenne, L., Bouchet, C., Kmecova, Z., Robillard, P., Guignabert, C., Tu, L., Delcambre, F., Marthan, R., Muller, B., Guibert, C., Freund-Michel, V. Tags: Pulmonary hypertension Source Type: research

Late Breaking Abstract - Involvement of Orai1 Ca2+ channel in the pathogenesis of pulmonary arterial hypertension. Orai1 as a new potential therapeutic target ?
Conclusion: Altogether our results provide proof of concept that Orai1 should be considered as a new therapeutic target in PAH.
Source: European Respiratory Journal - November 25, 2021 Category: Respiratory Medicine Authors: Masson, B., Le Ribeuz, H., Sabourin, J., Woodhouse, E., Foster, R., Ruchon, Y., Dutheil, M., Boët, A., Ghigna, M.-R., Mercier, O., Beech, D., Benitah, J.-P., Bailey, M., Humbert, M., Montani, D., Capuano, V., Antigny, F. Tags: Pulmonary hypertension Source Type: research

Haploid genetic screening identifies a novel regulator of BMPR2
Pulmonary arterial hypertension (PAH), is characterised by profound remodelling of small pulmonary arteries, leading to increased pulmonary arterial pressures and premature death by right heart failure. Heterozygous germ-line mutations in the bone morphogenetic protein type II receptor (BMPR2) cause ~70% of familial PAH and ~20% of idiopathic PAH cases. The majority of mutations lead to haploinsufficiency but crucially, regardless of the presence of mutation, lung BMPR2 expression is reduced in all forms of PAH. Therefore, restoration of BMPR2 levels is an important therapeutic target. We previously showed that BMPR2 ubiqu...
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Dunmore, B., Burr, S., Upton, P., Nathan, J., Morrell, N. Tags: Pulmonary hypertension Source Type: research

Protein truncating mutations in ATP13A3 promote pulmonary arterial hypertension
Conclusions: Our initial findings provide further evidence that loss of function mutations in ATP13A3 are directly involved in causation of PAH and the mechanism involves alterations in cellular polyamine levels.
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Legchenko, E., Liu, B., West, J., Vangheluwe, P., Upton, P., Morrell, N. Tags: Pulmonary hypertension Source Type: research

GCN2 regulates BMP signaling: consequence for PVOD pathobiology and therapeutic management
Conclusion: GCN2 loss-of-function negatively regulates SMAD1/5/9 phosphorylation. Despite this dampened BMP signaling, exogenous BMP9 was still able to reverse GCN2 inhibition-induced hPMEC proliferation. BMP9 may hence be considered as potential therapeutic options for PVOD
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Manaud, G., Lambert, M., Soilih, B., Girerd, B., Soubrier, F., Bignard, J., Claude, O., Lecerf, F., Florio, M., Sun, B., Nadaud, S., Verleden, S., Remy, S., Anegon, I., Mercier, O., Fadel, E., Simmoneau, G., Humbert, M., Montani, D., Antigny, F., Perros, Tags: Pulmonary hypertension Source Type: research

Regulation of Type I cytokine receptors as a target for pulmonary arterial hypertension treatment?
Conclusions: TypeIR intracellular trafficking regulation is altered in PAH patients compared to controls, due to a shift in USP8/RNF41 ratio. Restoring USP8/RNF41 ratio in PA-SMCs may represent a potential target in PAH.
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Jutant, E.-M., Tu, L., Le Vely, B., Thuillet, R., Humbert, M., Guignabert, C., Huertas, A. Tags: Pulmonary hypertension Source Type: research

Role of c-Abelson in the loss of genome integrity in endothelial cells in pulmonary arterial hypertension
Conclusions: Our results demonstrate a central role of c-Abl in the loss of DNA integrity in iPAH P-ECs.
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Le Vely, B., Berrebeh, N., Phan, C., Thuillet, R., Humbert, M., Huertas, A., Guignabert, C., Tu, L. Tags: Pulmonary hypertension Source Type: research

NGF induces pulmonary arterial hyperreactivity through connexin 43 increased expression
In conclusion, NGF pathway is upregulated in IPAH cells. NGF increases Cx43 PA expression through TrkA receptor. Cx43 increased expression at plasma membrane upregulates GAP junction activity, thus promoting PA hyperreactivity.
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Cardouat, g., Douard, M., Roubenne, L., Kmecova, Z., Robillard, P., Guignabert, C., Tu, L., Delcambre, F., Marthan, R., Muller, B., Guibert, C., Freund-Michel, V. Tags: Pulmonary hypertension Source Type: research

Late Breaking Abstract - The effects of BMPRII loss on endothelial shear adaptation in the pulmonary vascular endothelium
Conclusion: Reduced BMPRII expression may contribute to PAH by engendering abnormal pulmonary artery endothelial shear adaptation.
Source: European Respiratory Journal - November 20, 2019 Category: Respiratory Medicine Authors: Mahomed, A., Burke-Gaffney, A., Moledina, S., Wort, S. J. Tags: Pulmonary hypertension Source Type: research

Alternative Polyadenylation(APA) modulates extracellular matrix deposition in pulmonary hypertension
Cleavage and polyadenylation is an important and regulated step in the maturation of mRNAs. Alternative polyadenylation (APA) is typically a shortening of the 3’UTR of affected gene by using a second polyadenylation signal. This shortening can remove regulation and can lead to increased expression of these mRNAs. APA induced by the depletion of the 25kDa subunit of cleavage factor I (CFIm25) has been shown to affect transcripts encoding for extracellular matrix (ECM) Proteins. This leads to the hypothesis that APA due to reduced CFIm25 expression could play a role in modulating ECM production of pulmonary vasculature...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Collum, S., Weng, T., Hernandez, A., Mertens, T., Chen, N., Guha, A., Youker, K., Wagner, E., Han, L., Blackburn, M., Karmouty-Quintana, H. Tags: Pulmonary Hypertension Source Type: research

Late Breaking Abstract - NGF induces pulmonary arterial hyperreactivity through increased connexin-43 expression: potential role in pulmonary hypertension
Conclusions: Our results show that NGF increases Cx43 expression in human and rat PA through a TrkA/PI3K/ERK-dependent signalling pathway. This mechanism contributes to NGF-induced PA hyperreactivity and may thus participate in PH pathophysiology.
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Douard, M., Robillard, P., Deweirdt, J., Baudrimont, I., Dubois, M., Marthan, R., Savineau, J.-P., Muller, B., Guibert, C., Freund-Michel, V. Tags: Pulmonary hypertension Source Type: research

Late Breaking Abstract - Chronic Hypoxia Promotes Pulmonary Venous Smooth Muscle Cells Proliferation by Upregulating Calcium Sensing Receptor
Conclusions: CaSR mediating excessive PVSMC proliferation is a new pathogenic mechanism involved in the initiation and progression of hypoxic PVSMC proliferation.
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Peng, G., Li, S., Hong, W., Xu, J., Liu, R., Li, B., Ran, P. Tags: Pulmonary hypertension Source Type: research

The BRD4-PLK1 Axis Drives Vascular Remodeling in PAH
Conclusion: We demonstrate that the BRD4/PLK1 axis is increased in human PAH and represents a promising therapeutic target.
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Boucherat, O., Tremblay, E., Martineau, S., Jahagirdar, R., Kulikowski, E., Provencher, S., Bonnet, S. Tags: Pulmonary hypertension Source Type: research

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