Article
Veterinary Sciences
Satoshi Kameshima, Yuki Nakamura, Kenji Uehara, Tomoko Kodama, Hideyuki Yamawaki, Kotaro Nishi, Shozo Okano, Ryo Niijima, Yuya Kimura, Naoyuki Itoh
Summary: The aim of this study was to investigate the effects of riociguat on the contractility of the canine pulmonary artery and the hemodynamics of dogs with acute pulmonary hypertension (PH). It was found that riociguat can inhibit the elevation of pulmonary artery pressure in dogs with PH by increasing cGMP levels and reducing contraction induced by endothelin-1. Riociguat may be a novel and safe therapeutic agent for the treatment of PH in veterinary medicine.
VETERINARY SCIENCES
(2023)
Article
Neurosciences
Ellis Nelissen, Britt T. J. van Hagen, Elentina K. Argyrousi, Nick P. van Goethem, Pim R. A. Heckman, Dean Paes, Danielle A. J. Mulder-Jongen, Johannes G. Ramaekers, Arjan Blokland, Harald H. H. W. Schmidt, Jos Prickaerts
Summary: This study investigated the acute effects of riociguat, a soluble guanylate cyclase (sGC) stimulator, on memory function and neuronal plasticity in mice. The results showed that acute administration of low dose riociguat enhanced working memory, short-term memory, and long-term spatial memory. The memory-enhancing effects are likely regulated by peripheral effects on cyclic guanosine monophosphate (cGMP) signaling. However, further research is needed to explore the possible contribution of hemodynamic or metabolic effects of sGC stimulators on memory performance.
NEUROSCIENCE LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Maria Duszyn, Brygida Swiezawska-Boniecka, Aloysius Wong, Krzysztof Jaworski, Adriana Szmidt-Jaworska
Summary: Recent studies identified a novel receptor BdPepR2 in Brachypodium distachyon, showing both catalytic and kinase activity, with important implications for plant processes. Through bioinformatic analysis, a conserved core catalytic motif was designed, leading to the discovery of potential GCs in monocots.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Respiratory System
Raymond L. Benza, David Langleben, Anna R. Hemnes, Anton Vonk Noordegraaf, Stephan Rosenkranz, Thenappan Thenappan, Paul M. Hassoun, Ioana R. Preston, Stefano Ghio, Roberto Badagliacca, Carmine D. Vizza, Irene M. Lang, Christian Meier, Ekkehard Gruenig
Summary: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) can lead to right heart failure, with right ventricular changes as long-term indicators. Riociguat, an approved treatment for these diseases, is examined for its effects on right ventricular remodeling, function, and structural parameters in this review.
EUROPEAN RESPIRATORY REVIEW
(2022)
Review
Biology
Maryam Alfalasi, Sarah Alzaabi, Linda Ostlundh, Rami H. Al-Rifai, Suhail Al-Salam, Paul Michel Mertes, Seth L. Alper, Elhadi H. Aburawi, Abdelouahab Bellou
Summary: This systematic review assessed the effect of inhibiting nitric oxide pathways on blood pressure and survival in animal models of anaphylactic shock (AS). The results showed that inhibition of nitric oxide pathways improved survival and/or blood pressure in some experimental conditions. However, there is insufficient evidence to support the use of this approach as a definitive treatment for AS in humans.
Review
Cardiac & Cardiovascular Systems
Alberto Aimo, Vincenzo Castiglione, Giuseppe Vergaro, Giorgia Panichella, Michele Senni, Carlo Mario Lombardi, Michele Emdin
Summary: Heart failure with reduced or preserved ejection fraction is associated with significant morbidity and mortality, warranting the search for novel therapeutic agents. The nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway is disrupted in heart failure, and sGC activators or stimulators may be effective in treating this condition. Vericiguat has shown safety and efficacy in patients with HFrEF, but caution is needed in its use.
HEART FAILURE REVIEWS
(2022)
Article
Cardiac & Cardiovascular Systems
Theresa-Marie Dachs, Franz Duca, Rene Rettl, Christina Binder-Rodriguez, Daniel Dalos, Luciana Camuz Ligios, Andreas Kammerlander, Ekkehard Grunig, Ingrid Pretsch, Regina Steringer-Mascherbauer, Klemens Ablasser, Manfred Wargenau, Julia Mascherbauer, Irene M. Lang, Christian Hengstenberg, Roza Badr-Eslam, Johannes Kastner, Diana Bonderman
Summary: This study investigated the efficacy of riociguat, an oral soluble guanylate cyclase stimulator, in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF). The results showed that riociguat improved hemodynamics in PH-HFpEF but did not change clinical symptoms within the study period. There were some adverse events associated with riociguat, leading to more dropouts compared to placebo.
EUROPEAN HEART JOURNAL
(2022)
Article
Cardiac & Cardiovascular Systems
Wahiba Dhahri, Sylvie Dussault, Nozha Raguema, Michel Desjarlais, Alain Rivard
Summary: This study found that Riociguat, an sGC stimulator, promotes angiogenesis and improves neovascularization after ischemia. The mechanism involves the activation of the p44/p42 MAP kinase pathway and an increase in the number and functions of PACs. This discovery could potentially serve as a new therapeutic strategy for reducing tissue ischemia in patients with severe atherosclerotic diseases.
Article
Pediatrics
Regan E. Giesinger, Amy H. Stanford, Brady Thomas, Steven H. Abman, Patrick J. McNamara
Summary: The effects of riociguat, an oral-soluble guanylate-cyclase stimulator, were studied in 10 infants with chronic pulmonary arterial hypertension. Improvement in respiratory status, right heart dilation, function, and chronic pulmonary arterial hypertension were observed. There were decreases in systolic, diastolic, and mean arterial pressures, without any critical hypotension or hypoxemia.
JOURNAL OF PEDIATRICS
(2023)
Review
Cardiac & Cardiovascular Systems
Carlo Mario Lombardi, Giuliana Cimino, Matteo Pagnesi, Andrea Dell'Aquila, Daniela Tomasoni, Alice Ravera, Riccardo Inciardi, Valentina Carubelli, Enrico Vizzardi, Savina Nodari, Michele Emdin, Alberto Aimo
Summary: The NO-sGC-cGMP pathway plays a crucial role in cardiovascular function and is disrupted in heart failure. Both sGC activators and stimulators can modulate cGMP levels through different mechanisms, offering potential benefits for patients with heart failure.
CURRENT CARDIOLOGY REPORTS
(2021)
Article
Cardiac & Cardiovascular Systems
Mitsushige Murata, Takashi Kawakami, Masaharu Kataoka, Hidenori Moriyama, Takahiro Hiraide, Mai Kimura, Jin Endo, Takashi Kohno, Yuji Itabashi, Keiichi Fukuda
Summary: This study demonstrated that riociguat can improve cardiovascular conditions in patients with pulmonary hypertension, including enhancing cardiac output and right ventricular function. Echocardiography showed that riociguat can improve right ventricular structure and function in patients with varying degrees of pulmonary hypertension.
Article
Plant Sciences
Liqian Chen, Xinghong Zhou, Yijian Deng, Ying Yang, Xiaohu Chen, Qinghong Chen, Yanyan Liu, Xiuqiong Fu, Hiu Yee Kwan, Yanting You, Wen Jin, Xiaoshan Zhao
Summary: This study aimed to confirm the protective effects of ZWD on cardiac hypertrophy and explore the underlying mechanisms. The results showed that ZWD reduces oxidative stress and inflammation and exerts cardioprotective effects by activating the sGC-cGMP-PKG signaling pathway.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Masashi Tawa, Takashi Shimosato, Keisuke Nakagawa, Tomio Okamura, Mamoru Ohkita
Summary: This study found that renovascular hypertension did not affect the vasorelaxant responses mediated by NO-sensitive and NO-insensitive forms of sGC, suggesting that sGC may not be responsible for the reduced NO bioavailability observed during renovascular hypertension.
Article
Respiratory System
Bouchra Lamia, Jean Dallongeville, Lionel Bensimon, Antoinette Hakme, Mathilde Pouriel, Olivier Sitbon
Summary: This retrospective multicentric study aimed to describe the real-world utilization of riociguat in France. The results showed that riociguat is used in accordance with its therapeutic indication in France for the treatment of inoperable and persistent/recurrent post-surgery chronic thromboembolic pulmonary hypertension patients, and confirmed its long-term safety.
RESPIRATORY MEDICINE AND RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Susana S. Correia, Rajesh R. Iyengar, Peter Germano, Kim Tang, Sylvie G. Bernier, Chad D. Schwartzkopf, Jenny Tobin, Thomas W. -H. Lee, Guang Liu, Sarah Jacobson, Andrew Carvalho, Glen R. Rennie, Joon Jung, Paul A. Renhowe, Elisabeth Lonie, Christopher J. Winrow, John R. Hadcock, Juli E. Jones, Mark G. Currie
Summary: Effective treatments for neurodegenerative diseases are urgently needed as the global population ages. CY6463, a brain-penetrant sGC stimulator, has shown promise in preclinical models by improving neuronal activity, mediating neuroprotection, and enhancing cognitive performance.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Argen Mamazhakypov, Gayathri Viswanathan, Allan Lawrie, Ralph Theo Schermuly, Sudarshan Rajagopal
Summary: This review highlights the central role of inflammation in pulmonary arterial hypertension (PAH) and the regulation of chemokines and chemokine receptors in PAH and right ventricular remodeling. Studies have shown that pharmacological targeting of chemokines and receptors could be an effective therapeutic approach for PAH.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Environmental Sciences
Argen Mamazhakypov, Natascha Sommer, Birgit Assmus, Khodr Tello, Ralph Theo Schermuly, Djuro Kosanovic, Akpay Sh Sarybaev, Norbert Weissmann, Oleg Pak
Summary: RV function plays a critical role in the outcome of patients with pulmonary hypertension, but approved therapies for left ventricular failure are not established for RV. The direct effects of specific vasoactive drugs for pulmonary arterial hypertension on RV are still not fully investigated. The use of pulmonary artery banding (PAB) allows for independent study of RV failure pathogenesis and testing of potential therapies.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2021)
Article
Biochemistry & Molecular Biology
Niklas Mueller, Timothy Warwick, Kurt Noack, Pedro Felipe Malacarne, Arthur J. L. Cooper, Norbert Weissmann, Katrin Schroeder, Ralf P. Brandes, Flavia Rezende
Summary: ROS play a crucial role in cardiovascular signal transduction, with different types and concentrations leading to distinct metabolic and transcriptomic responses in endothelial cells. High levels of H2O2 significantly impact both metabolism and gene expression, while other ROS mainly affect gene expression levels.
Article
Biotechnology & Applied Microbiology
Michelle L. Woods, Astrid Weiss, Anna M. Sokol, Johannes Graumann, Thomas Boettger, Antje M. Richter, Ralph T. Schermuly, Reinhard H. Dammann
Summary: Silencing of the AATK gene has been observed in various cancers and is associated with decreased patient survival. In this study, we found that DNA methyltransferase inhibitors can reactivate AATK, while epigenetic targeting inhibits its expression. We also discovered that AATK is a Ser/Thr kinase that phosphorylates TP53, and its kinase activity is important for growth suppression and regulation of cell cycle regulators. These findings suggest that AATK acts as an epigenetically inactivated tumor suppressor gene.
CANCER GENE THERAPY
(2022)
Letter
Respiratory System
Philipp Douschan, Khodr Tello, Andreas J. Rieth, Christoph B. Wiedenroth, Teresa Sassmann, Gabor Kovacs, Hossein A. Ghofrani, Werner Seeger, Manuel Richter, Stefan Guth
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Medicine, General & Internal
Natascha Sommer, Finn Fabian Theine, Oleg Pak, Khodr Tello, Manuel Richter, Henning Gall, Jochen Wilhelm, Rajkumar Savai, Norbert Weissmann, Werner Seeger, Hossein A. Ghofrani, Matthias Hecker
Summary: The study found that mitochondrial function in PBMC of PAH patients is affected by disease severity, with mitochondrial respiration correlating with hemodynamic parameters. Further research is needed to investigate cell-type-specific alterations and functional consequences.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Cell Biology
Stefan Kuhnert, Siavash Mansouri, Michael A. Rieger, Rajkumar Savai, Edibe Avci, Gabriela Diaz-Pina, Manju Padmasekar, Mario Looso, Stefan Hadzic, Till Acker, Stephan Klatt, Jochen Wilhelm, Ingrid Fleming, Natascha Sommer, Norbert Weissmann, Claus Vogelmeier, Robert Bals, Andreas Zeiher, Stefanie Dimmeler, Werner Seeger, Soni S. Pullamsetti
Summary: This study found an increased incidence of CHIP mutations in COPD patients, which are associated with hypomethylation of PLD5, leading to elevated levels of glycerol phosphocholine, pro-inflammatory cytokines, and deteriorating lung function.
Article
Cell Biology
Akylbek Sydykov, Aleksandar Petrovic, Abdirashit M. Maripov, Marija Gredic, Daniel Gerd Bermes, Nadira Kushubakova, Kubatbek Muratali Uulu, Christina Pilz, Meerim Cholponbaeva, Melis Duishobaev, Samatbek Satybaldyev, Nurgul Satieva, Argen Mamazhakypov, Meerim Sartmyrzaeva, Nazgul Omurzakova, Zhainagul Kerimbekova, Nursultan Baktybek, Cholpon Kulchoroeva, Oleg Pak, Lan Zhao, Norbert Weissmann, Sergey Avdeev, Leonid N. Maslov, Hossein Ardeschir Ghofrani, Ralph Theo Schermuly, Akpay S. Sarybaev, Djuro Kosanovic
Summary: This study investigates the role of microparticles (MPs) and cold exposure in high altitude pulmonary hypertension (HAPH). The results show that long-term exposure to cold environment is associated with increased pulmonary artery pressure in high-altitude residents, and the circulating levels of MPs differ between lowlanders and HAPH highlanders during the colder season.
Article
Respiratory System
Rogerio Souza, David B. Badesch, H. Ardeschir Ghofrani, J. Simon R. Gibbs, Mardi Gomberg-Maitland, Vallerie V. Mclaughlin, Ioana R. Preston, Aaron B. Waxman, Ekkehard Gruenig, Grzegorz Kope, Gisela Meyer, Karen M. Olsson, Stephan Rosenkranz, Jianxin Lin, Amy O. Johnson-Levonas, Janethe de Oliveira Pena, Marc Humbert, Marius M. Hoeper
Summary: Sotatercept demonstrated significant improvements in pulmonary artery pressure and right heart function in pre-treated patients with pulmonary arterial hypertension (PAH).
EUROPEAN RESPIRATORY JOURNAL
(2023)
Article
Cardiac & Cardiovascular Systems
Zvonimir A. Rako, Athiththan Yogeswaran, Balint K. Lakatos, Alexandra Fabian, Selin Yildiz, Bruno Brito da Rocha, Istvan Vadasz, Hossein Ardeschir Ghofrani, Werner Seeger, Henning Gall, Nils C. Kremer, Manuel J. Richter, Pascal Bauer, Ryan J. Tedford, Robert Naeije, Attila Kovacs, Khodr Tello
Summary: This study aimed to assess the relationship between right ventricular contraction pattern and right ventricular-pulmonary arterial (RV-PA) coupling. The results showed that early RV-PA uncoupling is associated with reduced longitudinal function, while advanced uncoupling leads to reduced anteroposterior movement and left ventricular preload. These findings are important for risk assessment in patients.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2023)
Article
Respiratory System
Athiththan Yogeswaran, Zvonimir A. Rako, Selin Yildiz, Hossein Ardeschir Ghofrani, Werner Seeger, Bruno Brito da Rocha, Henning Gall, Nils C. Kremer, Philipp Douschan, Silvia Papa, Carmine Dario Vizza, Domenico Filomena, Ryan J. Tedford, Robert Naeije, Manuel J. Richter, Roberto Badagliacca, Khodr Tello
Summary: Our study demonstrates the usefulness of echocardiography-derived S'/RAAi for noninvasive assessment of RV diastolic function and prognosis in PH.
Review
Biochemistry & Molecular Biology
Soni Savai Pullamsetti, Ravikumar Sitapara, Robin Osterhout, Astrid Weiss, Laura L. Carter, Lawrence S. Zisman, Ralph Theo Schermuly
Summary: Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling and increased pulmonary vascular resistance. Histologically, PAH is characterized by plexiform and neointimal lesions composed of dysregulated endothelial cells and myofibroblasts. The PDGFR-CSF1R-c-KIT signaling network has been implicated in PAH pathogenesis, and inhibition of this network has potential therapeutic benefits. Seralutinib, which targets these pathways, shows promise for the treatment of PAH.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biophysics
Milad Eyvazi Hesar, Niloofar Sadat Seyedsadrkhani, Dibyendu Khan, Adib Naghashian, Mateusz Piekarski, Henning Gall, Ralph Schermuly, Hossein Ardeschir Ghofrani, Sven Ingebrandt
Summary: This research presents a wearable epidermal electronic system for continuous monitoring of a prognostic parameter for hypertension. The system is flexible, wireless, and smartphone-enabled, allowing real-time monitoring of electrocardiograms and seismocardiograms. The system shows promising performance in predicting hypertension.
BIOSENSORS & BIOELECTRONICS
(2023)
Article
Cardiac & Cardiovascular Systems
Marc Humbert, Gabor Kovacs, Marius M. Hoeper, Roberto Badagliacca, Rolf M. F. Berger, Margarita Brida, Jorn Carlsen, Andrew J. S. Coats, Pilar Escribano-Subias, Pisana Ferrari, Diogenes S. Ferreira, Hossein Ardeschir Ghofrani, George Giannakoulas, David G. Kiely, Eckhard Mayer, Gergely Meszaros, Blin Nagavci, Karen M. Olsson, Joanna Pepke-Zaba, Jennifer K. Quint, Goran Radegran, Gerald Simonneau, Olivier Sitbon, Thomy Tonia, Mark Toshner, Jean-Luc Vachiery, Anton Vonk Noordegraaf, Marion Delcroix, Stephan Rosenkranz, Markus Schwerzmann, Anh-Tuan Dinh-Xuan, Andy Bush, Magdy Abdelhamid, Victor Aboyans, Eloisa Arbustini, Riccardo Asteggiano, Joan-Albert Barbera, Maurice Beghetti, Jelena Celutkiene, Maja Cikes, Robin Condliffe, Frances de Man, Volkmar Falk, Laurent Fauchier, Sean Gaine, Nazzareno Galie, Wendy Gin-Sing, John Granton, Ekkehard Gruenig, Paul M. Hassoun, Merel Hellemons, Tiny Jaarsma, Barbro Kjellstrom, Frederikus A. Klok, Aleksandra Konradi, Konstantinos C. Koskinas, Dipak Kotecha, Irene Lang, Basil S. Lewis, Ales Linhart, Gregory Y. H. Lip, Maja-Lisa Lochen, Alexander G. Mathioudakis, Richard Mindham, Shahin Moledina, Robert Naeije, Eva Prescott, Amina Rakisheva, Abilio Reis, Arsen D. Ristic, Jens Cosedis Nielsen, Horst Olschewski, Isabelle Opitz, Steffen E. Petersen
GIORNALE ITALIANO DI CARDIOLOGIA
(2023)
