Article
Pharmacology & Pharmacy
Chunhua Fu, Yuanqing Lu, Mason A. Williams, Mark L. Brantly, Corey E. Ventetuolo, Laurence M. Morel, Borna Mehrad, Edward W. Scott, Andrew J. Bryant
Summary: The study investigated the impact of myeloid cell proliferation induced by emergency myelopoiesis on the development of pulmonary hypertension, as well as the therapeutic effect of PD-L1 in preventing pulmonary vascular remodeling. The results showed that PD-L1 could be a viable therapeutic target in pulmonary hypertension by acting through a signaling axis involving myeloid-derived suppressor cells.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Xia Xu, Hua Feng, Chaochao Dai, Weida Lu, Jun Zhang, Xiaosun Guo, Qihui Yin, Jianli Wang, Xiaopei Cui, Fan Jiang
Summary: The study showed that CX-5461 had good tolerance for in vivo treatments in rats with PAH, preventing pulmonary arterial remodelling, perivascular inflammation, and pulmonary hypertension, leading to improved survival. In vivo and in vitro experiments demonstrated that CX-5461 induced cell cycle arrest in human pulmonary arterial smooth muscle cells through increased activation of p53, suggesting that pharmacological inhibition of Pol I could be a novel therapeutic strategy for drug-resistant PAH.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Olga Mulas, Giovanni Caocci, Brunella Mola, Giorgio La Nasa
Summary: This study found that hypertension is a common cardiovascular complication in CML patients treated with second- or third-generation TKI. Compared to the first-generation imatinib, nilotinib and ponatinib were both associated with a significantly increased risk of hypertension.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Irene Martin de Miguel, Alejandro Cruz-Utrilla, Eduardo Oliver, Pilar Escribano-Subias
Summary: Pulmonary arterial hypertension (PAH) is a severe condition with a high mortality rate. Despite advances in diagnostic and therapeutic strategies, current treatments mainly focus on pulmonary vasodilation and do not address the pathological changes in the pulmonary vasculature. This review discusses the molecular mechanisms involved in PAH, the development of novel therapeutic compounds, and their potential role in future PAH treatment algorithms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, Research & Experimental
James May, Jane A. Mitchell, R. Gisli Jenkins
Summary: Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung with limited treatment options. This article proposes that vascular and endothelial cell abnormalities play a significant role in the pathobiology of IPF and calls for a comprehensive evaluation of these dysregulated pathways to find effective therapies and a cure for this devastating disease.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Peripheral Vascular Disease
Harri Elamaa, Mika Kaakinen, Marjut Natynki, Zoltan Szabo, Veli-Pekka Ronkainen, Ville Aijala, Joni M. Maki, Risto Kerkela, Johanna Myllyharju, Lauri Eklund
Summary: The study suggests that inducible deletion of PHD2 in endothelial cells can lead to progressive lung disease, while deletion in arterial smooth muscle cells results in elevated right ventricular pressure without alterations in vascular tone regulators. Mechanistically, PHD2 inhibition in smooth muscle cells involves actin polymerization-related tension development via activated cofilin.
Review
Cell Biology
France Dierick, Julien Solinc, Juliette Bignard, Florent Soubrier, Sophie Nadaud
Summary: This review summarizes the importance of cellular processes and dysfunction in the development of pulmonary arterial hypertension, as well as the roles of circulating and resident vascular cells in pulmonary vascular remodeling.
Article
Biochemistry & Molecular Biology
Benjamin Le Vely, Carole Phan, Nihel Berrebeh, Raphael Thuillet, Mina Ottaviani, Mustapha Kamel Chelgham, Marie-Camille Chaumais, Larbi Amazit, Marc Humbert, Alice Huertas, Christophe Guignabert, Ly Tu
Summary: This study found that cAbl concentrations were lower in the endothelium of remodeled pulmonary vessels in patients with PAH. In vitro and in vivo experiments showed that PAH-ECs had lower cAbl expression and activity, as well as altered DNA damage response and capacity of tube formation. Downregulation of cAbl resulted in genomic instability and the failure to form tubes, while upregulation of cAbl reduced DNA damage and apoptosis in PAH-ECs.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Richard Mprah, Gabriel Komla Adzika, Yusif I. Gyasi, Marie Louise Ndzie Noah, Joseph Adu-Amankwaah, Adebayo O. Adekunle, Maxwell Duah, Prosperl Ivette Wowui, Qiao Weili
Summary: Pulmonary arterial hypertension is a severe disease characterized by chronic pulmonary hypertension. Current treatments focus on regulating the balance of vasodilation/vasoconstriction, but are unable to stop disease progression. Recent studies suggest that metabolic dysregulation, particularly increased glutamine metabolism, may play a role in driving PAH progression.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Review
Physiology
Ke-Xue Li, Zi-Chao Wang, Jeremiah Ong'Achwa Machuki, Meng-Zhen Li, Yu-Jie Wu, Ming-Kai Niu, Kang-Ying Yu, Qing-Bo Lu, Hai-Jian Sun
Summary: Hypertension is a leading cause of cardiovascular morbidity and mortality, and curcumin, a phytochemical derived from turmeric, shows promise in treating hypertension-induced vascular remodeling.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Iona Cuthbertson, Nicholas W. Morrell, Paola Caruso
Summary: Pulmonary arterial hypertension (PAH) is the most severe type of pulmonary hypertension, characterized by progressive remodeling of peripheral pulmonary arteries. Endothelial cell dysfunction is a key trigger, leading to vascular remodeling, increased pressure, and right ventricular hypertrophy. Abnormal cellular molecular signatures and loss-of-function mutations in the BMPR2 gene contribute to PAH pathophysiology. Metabolic abnormalities, including glycolytic reprogramming and mitochondrial dysfunction, are observed in various tissues and may affect treatment response. This review critically discusses the mechanisms linking metabolic abnormalities with dysfunctional BMPR2 signaling and their relevance to PAH pathogenesis and potential therapies.
CIRCULATION RESEARCH
(2023)
Review
Medicine, General & Internal
Anna Foley, Benjamin E. Steinberg, Neil M. Goldenberg
Summary: Inflammasomes are multi-protein complexes that sense inflammatory stimuli and play a role in various pulmonary diseases, including pulmonary arterial hypertension (PAH). Understanding the activation of inflammasome in immune and vascular cells is important for the development of potential therapeutic targets for PAH.
FRONTIERS IN MEDICINE
(2022)
Article
Cell Biology
Haiyan Deng, Xiaoxue Tian, Hening Sun, Huan Liu, Meili Lu, Hongxin Wang
Summary: This study demonstrates that Calpain-1 plays a crucial role in hypoxia-induced pulmonary vascular remodeling and fibrosis through HIF-1 alpha, providing a better understanding of the pathogenesis of hypoxic pulmonary hypertension.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Biology
Sunil Jit R. J. Logantha, Tomoko T. Yamanushi, Mais Absi, Ian P. Temple, Hideaki Kabuto, Eiichiro Hirakawa, Gillian Quigley, X. Zhang, Alison M. Gurney, George Hart, Henggui Zhang, Halina Dobrzynski, Mark R. Boyett, Joseph Yanni
Summary: Patients with pulmonary arterial hypertension (PAH) exhibit sinus node dysfunction, which is characterized by a decrease in heart rate and arrhythmias. In a rat model of PAH, there were changes in ion channels, Ca2+-handling genes, and fibrosis genes in the sinus node, providing an explanation for the dysfunction.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Cell Biology
Peter Braubach, Christopher Werlein, Stijn E. Verleden, Isabell Maerzke, Jens Gottlieb, Gregor Warnecke, Sabine Dettmer, Florian Laenger, Danny Jonigk
Summary: This article discusses the range of fibroelastotic changes in pulmonary tissue and proposes stringent histological criteria to distinguish clinically relevant variants. Through systematic evaluation of lung specimens, novel in-transit and activity stages of fibroelastotic remodeling were identified. This comprehensive definition provides a basis for patient stratification and prediction of outcome.
Article
Rheumatology
Sebastien Sanges, Lisa Rice, Ly Tu, Eleanor Valenzi, Jean-Luc Cracowski, David Montani, Julio C. Mantero, Camille Ternynck, Guillemette Marot, Andreea M. Bujor, Eric Hachulla, David Launay, Marc Humbert, Christophe Guignabert, Robert Lafyatis
Summary: This study examined the serum proteome of patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) and identified two proteins that were significantly correlated with pulmonary vascular resistance (PVR), potentially providing biomarkers for earlier diagnosis and treatment.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Respiratory System
Athenais Boucly, Ly Tu, Christophe Guignabert, Christopher Rhodes, Pascal De Groote, Gregoire Prevot, Emmanuel Bergot, Arnaud Bourdin, Antoine Beurnier, Anne Roche, Mitja Jevnikar, Xavier Jais, David Montani, Martin R. Wilkins, Marc Humbert, Olivier Sitbon, Laurent Savale
Summary: In this study, a three-biomarker panel consisting of beta-NGF, CXCL9, and TRAIL in serum was identified to be independently associated with prognosis in patients with PAH. These biomarkers showed stronger prognostic value for survival compared to conventional non-invasive variables such as NYHA Functional Class, 6-min walk distance, and BNP/NT-proBNP. The results were validated in an independent external validation cohort.
EUROPEAN RESPIRATORY JOURNAL
(2023)
Article
Cardiac & Cardiovascular Systems
Christophe Guignabert, Laurent Savale, Athenais Boucly, Raphael Thuillet, Ly Tu, Mina Ottaviani, Christopher J. Rhodes, Pascal De Groote, Gregoire Prevot, Emmanuel Bergot, Arnaud Bourdin, Luke S. Howard, Elie Fadel, Antoine Beurnier, Anne Roche, Mitja Jevnikar, Xavier Jais, David Montani, Martin R. Wilkins, Olivier Sitbon, Marc Humbert
Summary: Activin A and FSTL3 serum levels are associated with transplant-free survival in PAH. They can serve as prognostic biomarkers for PAH, and their diagnostic values have been confirmed in an independent validation cohort. The activin signaling system in PAH involves phosphorylated Smad2/3 nuclear accumulation and differential immunoreactivities of various proteins in vascular endothelial and smooth muscle layers.
Article
Pharmacology & Pharmacy
Heba Abdelazeem, Ly Tu, Raphael Thuillet, Mina Ottaviani, Achraf Boulfrad, Thomas Beck, Amira Senbel, Salma Mani, Yves Castier, Alice Guyard, Alexy Tran-Dinh, Jamel El-Benna, Dan Longrois, Adam M. Silverstein, Christophe Guignabert, Xavier Norel
Summary: The study found that metformin treatment can slow down the progression of monocrotaline-induced pulmonary hypertension in rats and protect lung tissue by increasing endothelial nitric oxide synthase activity and protein kinase G-1 expression. In addition, AMPK activation can reduce vasoconstriction in patients with pulmonary hypertension. This study suggests that AMPK activation can enhance the nitric oxide pathway, alleviate vasoconstriction through direct effects on smooth muscles, and reverse pulmonary hypertension in rats.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Editorial Material
Respiratory System
Frances S. de Man, Anton Vonk Noordegraaf
EUROPEAN RESPIRATORY JOURNAL
(2023)
Letter
Respiratory System
Erik Asmus, Weronika Karle, Markus C. Brack, Corey Wittig, Felix Behrens, Leander Reinshagen, Moritz Pfeiffer, Sabrina Schulz, Bertina Mandzimba-Maloko, Lasti Erfinanda, Paul L. Perret, Laura Michalick, Patrick J. Smeele, Endry H. T. Lim, Charissa E. van den Brom, Alexander B. A. Vonk, Toralf Kaiser, Norbert Suttorp, Stefan Hippenstiel, Leif E. Sander, Florian Kurth, Ursula Rauch, Ulf Landmesser, Arash Haghikia, Robert Preissner, Harm J. Bogaard, Martin Witzenrath, Wolfgang M. Kuebler, Robert Szulcek, Szandor Simmons
EUROPEAN RESPIRATORY JOURNAL
(2023)
Article
Respiratory System
F. Robert, N. Berrebeh, C. Guignabert, M. Humbert, S. Bailly, L. Tu, L. Savale
Summary: This article provides a comprehensive review of the implication of the BMP-9/BMPR-II/ALK1/endoglin pathway in the pathophysiology of vascular diseases such as pulmonary arterial hypertension, hereditary hemorrhagic telangiectasia, and hepatopulmonary syndrome.
REVUE DES MALADIES RESPIRATOIRES
(2023)
Article
Cardiac & Cardiovascular Systems
Mohammad Arkani, Azar Kianzad, Samara Jansen, Josien Smit, Edward Post, Jip Ramaker, Tonny Lagerweij, Sjors G. J. G. In't Veld, David P. Noske, Anton Vonk Noordegraaf, Thomas Wurdinger, Myron G. G. Best, Harm-Jan Bogaard
Summary: This study demonstrates that analyzing platelet-derived RNA can accurately discriminate between pre- and postcapillary PH. By using particle swarm optimization and support vector machine algorithms, a panel of 1618 distinctive RNAs with differential levels was identified to accurately distinguish between the two types of PH.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Cell Biology
Matthieu Leuillier, Valentin Platel, Ly Tu, Guillaume Feugray, Raphael Thuillet, Deborah Groussard, Hind Messaoudi, Mina Ottaviani, Mustapha Chelgham, Lionel Nicol, Paul Mulder, Marc Humbert, Vincent Richard, Christophe Morisseau, Valery Brunel, Thomas Duflot, Christophe Guignabert, Jeremy Bellien
Summary: Inhibitors of soluble epoxide hydrolase (sEH) present an opportunity for developing oral drugs for cardiovascular and inflammatory diseases. However, the administration of sEH inhibitors may lead to the development of pulmonary hypertension (PH). This study evaluated the impact of chronic oral administration of the sEH inhibitor TPPU on hemodynamics and pulmonary vascular remodeling in rats. The results showed that TPPU did not induce or aggravate PH and RV dysfunction, and may have a potential beneficial effect against pulmonary artery remodeling in humans.
Article
Engineering, Biomedical
Tom C. L. Bracco Gartner, Ye Wang, Laurynas Leiteris, Iris van Adrichem, Judith Marsman, Marie Jose Goumans, Carlijn V. C. Bouten, Joost P. G. Sluijter, Jaap M. J. den Toonder, Willem J. L. Suyker, Jesper Hjortnaes
Summary: Cardiac fibroblasts in the ever-beating human heart remain quiescent due to the antifibrotic effect of cyclic strain conditions revealed by a novel platform for studying cardiac fibrosis-on-a-chip. This study provides insights into the mechanosensitive pathways and genes involved in the fibrogenic process, which can contribute to the development of new therapies against cardiac fibrosis.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2023)
Article
Oncology
Nicole E. Billingy, Vashti N. M. F. Tromp, Neil K. Aaronson, Rianne J. A. Hoek, Harm Jan Bogaard, Bregje D. Onwuteaka-Philipsen, Lonneke van de Poll-franse, Jacqueline G. Hugtenburg, Jose Belderbos, Annemarie Becker-Commissaris, Corina J. G. van den Hurk, Iris Walraven, N. C. van Walree, K. de Jaeger, S. Samii, W. Y. Lam-Wong, F. Koppe, J. A. Stigt, G. J. M. Herder, A. Welling, O. C. J. Schuurbiers-Siebers, J. M. Smit, A. J. van den Brekel, W. K. de Jong
Summary: This study compared the effect of reactive and active approaches in monitoring patient-reported outcome measures (PROMs) for lung cancer patients. The results showed that weekly PRO symptom monitoring significantly improved health-related quality of life (HRQOL) in these patients, with the reactive approach being more suitable for implementation.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Rheumatology
Jerome Avouac, Anne Cauvet, Cindy Orvain, Morgane Boulch, Francoise Tilotta, Ly Tu, Raphael Thuillet, Mina Ottaviani, Christophe Guignabert, Philippe Bousso, Yannick Allanore
Summary: This study aimed to investigate the efficacy of two B cell depletion strategies, including CD19-targeted CAR T cells, in a preclinical model of severe lung damages observed in systemic sclerosis. The study evaluated B cell depletion strategies in Fra-2 Tg mice. The results showed that CD19-targeted CAR-T cells in combination with anti-CD20 monoclonal antibody achieved deeper B cell depletion compared to anti-CD20 monoclonal antibody alone in both peripheral blood and lesional lungs of Fra-2 Tg mice. However, CAR-T cell infusion worsened the clinical score and increased mortality in Fra-2 Tg mice. CAR-T cell infusion also resulted in increased lung collagen content, histological fibrosis score, and right ventricular systolic pressure. CAR-T cells accumulated in lesional lungs and promoted T activation and inflammatory cytokine production. On the other hand, treatment with anti-CD20 monoclonal antibody alone had no impact on lung inflammation-driven fibrosis and pulmonary hypertension.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Critical Care Medicine
Marc Humbert, Olivier Sitbon, Christophe Guignabert, Laurent Savale, Athenais Boucly, Melanie Gallant-Dewavrin, Vallerie Mclaughlin, Marius M. Hoeper, Jason Weatherald
Summary: Summary: Pulmonary arterial hypertension (PAH) is a severe and treatable form of pre-capillary pulmonary hypertension caused by pulmonary vascular remodelling. Advances in basic science, clinical trials, real-world studies, and clinical practice guidelines have improved treatment options and outcomes for PAH patients. However, there is still a need for transformative innovations and novel therapeutic approaches to improve survival rates.
LANCET RESPIRATORY MEDICINE
(2023)
Article
Health Care Sciences & Services
Nadia Baalbaki, Jelle M. Blankestijn, Mahmoud I. Abdel-Aziz, Jan de Backer, Somayeh Bazdar, Ines Beekers, Rosanne J. H. C. G. Beijers, Joop P. van den Bergh, Lizan D. Bloemsma, Harm Jan Bogaard, Job J. M. H. van Bragt, Vera van den Brink, Jean Paul Charbonnier, Merel E. B. Cornelissen, Yennece Dagelet, Elin Haf Davies, Anne M. van der Does, George S. Downward, Cornelis M. van Drunen, Debbie Gach, J. J. Miranda Geelhoed, Jorrit Glastra, Kornel Golebski, Irene H. Heijink, Judith C. S. Holtjer, Sebastiaan Holverda, Laura Houweling, John J. L. Jacobs, Renee Jonker, Renate Kos, Ramon C. J. Langen, Ivo van der Lee, Asabi Leliveld, Firdaus A. A. Mohamed Hoesein, Anne H. Neerincx, Lieke Noij, Johan Olsson, Marianne van de Pol, Simon D. Pouwels, Emiel Rolink, Michael Rutgers, Havva Sahin, Daphne Schaminee, Annemie M. W. J. Schols, Lisanne Schuurman, Gitte Slingers, Olie Smeenk, Brigitte Sondermeijer, Paul J. Skipp, Marisca Tamarit, Inge Verkouter, Roel Vermeulen, Rianne de Vries, Els J. M. Weersink, Marco van de Werken, Yolanda de Wit-van Wijck, Stewart Young, Esther J. Nossent, Anke H. van der Zee
Summary: The P4O2 COVID-19 study aims to identify long COVID patients at risk for developing chronic lung disease and to find personalized therapeutic strategies. The study showed persistent symptoms and abnormalities in post-COVID patients, with the most commonly reported symptoms being respiratory and neurological symptoms.
JOURNAL OF PERSONALIZED MEDICINE
(2023)