Article
Biochemistry & Molecular Biology
Armin Muminovic, Yuliy Y. Chirkov, John D. Horowitz
Summary: Impairment of NO/sGC signalling is associated with cardiovascular disease and loss of anti-aggregatory function. This study demonstrates that sGC stimulators or activators may normalize NO/sGC homeostasis in platelets. Results show that these drugs can restore the impaired anti-aggregatory function in patients with NO/sGC signalling impairment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Rui Liu, Yunlu Kang, Lei Chen
Summary: The authors present structures of human sGC in complex with NO and sGC stimulators or activator, shedding light on the mechanism of sGC activation by pharmacological compounds.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Robert J. Smith, Cristina Perez-Ternero, Daniel Conole, Capucine Martin, Samuel H. Myers, Adrian J. Hobbs, David L. Selwood
Summary: C-type natriuretic peptide (CNP) regulates vascular homeostasis through NPR-C, which could serve as a novel therapeutic target for cardiovascular diseases. Small molecules designed and synthesized show promising biological activity, with lead compound 1 identified as a potent agonist with potential in vivo pharmacokinetic properties.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Peter Sandner, Markus Follmann, Eva Becker-Pelster, Michael G. Hahn, Christian Meier, Cecilia Freitas, Lothar Roessig, Johannes-Peter Stasch
Summary: The discovery of soluble GC (sGC) stimulators and sGC activators has provided valuable tools for understanding NO-sGC signaling and has led to new pharmacological opportunities for cardiovascular indications. Approved for pulmonary hypertension and heart failure, these compounds enhance sGC activity independently of NO and have unique therapeutic potential.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Xiao-Yan Jia, Yong-Ming Liu, Yong-Fei Wang, Jin-Yang An, Ke-Ling Peng, Hua Wang
Summary: This study examined the trends and hotspots in cardiovascular research on soluble guanylate cyclase (sGC) stimulators by analyzing publications retrieved from the Web of Science Core Collection. The results showed a gradual increase in the overall volume of publications in this field. The study also identified the leading driving force, top authors, and main research hotspots in CV research on sGC stimulators. The findings suggested that the treatment of heart failure, especially heart failure with preserved ejection fraction, may be the current and future research focus in this area.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Javed Butler, Muhammad Shariq Usman, Kevin J. Anstrom, Robert O. Blaustein, Marc P. Bonaca, Justin A. Ezekowitz, Cecilia Freitas, Carolyn S. P. Lam, Eldrin F. Lewis, JoAnn Lindenfeld, Ciaran J. McMullan, Robert J. Mentz, Christopher O'Connor, Giuseppe M. C. Rosano, Clara Ines Saldarriaga, Michele Senni, James Udelson, Adriaan A. Voors, Faiez Zannad
Summary: Patients with heart failure with reduced ejection fraction (HFrEF) have a high residual risk of adverse outcomes. Soluble guanylate cyclase (sGC) stimulators, such as vericiguat, may have the potential to lower this risk. However, further research is needed to evaluate the effects of vericiguat in low-risk HFrEF patients.
EUROPEAN JOURNAL OF HEART FAILURE
(2022)
Review
Cardiac & Cardiovascular Systems
Wei-Lin Liang, Bo Liang
Summary: This review summarizes the current research on soluble guanylate cyclase activators and stimulators in patients with heart failure, providing a reference for the discovery of these compounds.
CURRENT CARDIOLOGY REPORTS
(2023)
Article
Chemistry, Medicinal
Kevin M. Gayler, Jeremy M. Quintana, Jordan Mattke, Michael A. Plunk, Jessica H. Kostyo, Johann W. Karunananthan, Harold Nguyen, Mina Shuda, Liam D. Ferreira, Hannah Baker, Alexandra L. Stinchcomb, Iraida Sharina, Robert R. Kane, Emil Martin
Summary: Previous studies have shown that the anti-hyperlipidemic drug gemfibrozil can activate the NO receptor soluble guanylyl cyclase independently of NO and heme. New gemfibrozil derivatives were synthesized and evaluated for sGC activation, identifying positions in gemfibrozil's structure that are important for activation. Compounds 7c and 15b were found to be more potent activators of purified sGC's cGMP-forming activity compared to gemfibrozil, showing enhanced relaxation of preconstricted mouse thoracic aorta rings. These findings provide insights for further optimization of sGC activators based on the gemfibrozil scaffold.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ellis Nelissen, Elentina K. Argyrousi, Nick P. Van Goethem, Fuqiang Zhao, Catherine D. G. Hines, Gayathri Swaminath, Michael Gerisch, Joerg Hueser, Peter Sandner, Jos Prickaerts
Summary: The study found that the sGC stimulator vericiguat can enhance long-term memory by increasing hippocampal plasticity and promoting the translocation of oc-AMPA receptors to the cell membrane, while having no effect on blood pressure and cerebral blood volume. Stimulation of sGC may provide a new therapeutic strategy for treating VCI.
Article
Pharmacology & Pharmacy
Frank Wunder, Johannes-Peter Stasch, Andreas Knorr, Thomas Mondritzki, Damian Brockschnieder, Eva-Maria Becker-Pelster, Peter Sandner, Hanna Tinel, Gorden Redlich, Ingo V. V. Hartung, Alexandros Vakalopoulos, Markus Follmann
Summary: A new sGC stimulator, BAY-747, was discovered through high-throughput screening. BAY-747 exhibited high potency in vitro and had a long-lasting pharmacokinetic profile. Experimental results in animal models showed that BAY-747 had a good therapeutic effect on hypertension and resistant hypertension.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Elizabeth C. Wittenborn, Michael A. Marletta
Summary: sGC functions as the prototypical nitric oxide receptor in humans and other higher eukaryotes, transducing NO signals into cGMP for various physiological effects. Recent advancements in cryo-EM have allowed for the visualization of full-length sGC structures, providing valuable insights into sGC activation mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Wu Yang, Hao He, Tongtong Wang, Nan Su, Feng Zhang, Kai Jiang, Jing Zhu, Chonghe Zhang, Kongyan Niu, Luyue Wang, Xiaodong Yuan, Nan Liu, Lingjie Li, Wu Wei, Junhao Hu
Summary: The study found that in liver fibrosis, HSCs undergo significant transcriptomic changes rather than PFs, and HSCs are the exclusive source of myofibroblasts in CCL4-treated livers, while PFs are the major source in early cholestatic liver fibrosis. Single-cell RNA sequencing and lineage-tracing analysis uncovered differential gene-expression features between HSCs and PFs, providing evidence that these differences should be considered in developing antifibrotic therapeutic strategies.
Article
Medicine, Research & Experimental
Daisuke Gotoh, Nailong Cao, Eduardo C. Alexandre, Tetsuichi Saito, Yosuke Morizawa, Shunta Hori, Makito Miyake, Kazumasa Torimoto, Kiyohide Fujimoto, Naoki Yoshimura
Summary: This study examined the effects of low-dose insulin and a soluble guanylate cyclase activator on lower urinary tract dysfunction in rats with diabetes mellitus. The results suggest that sGC activation could be an effective treatment for LUTD in diabetes.
Article
Pharmacology & Pharmacy
Miguel A. Olivencia, Erika Esposito, Vincenzo Brancaleone, Sigismondo Castaldo, Giuseppe Cirino, Francisco Perez-Vizcaino, Raffaella Sorrentino, Roberta d'Emmanuele di Villa Bianca, Emma Mitidieri
Summary: This study explores the regulation of the redox state of soluble guanylate cyclase (sGC) by endogenous hydrogen sulfide (H2S). Lack of endogenous H2S disrupts the eNOS/NO/sGC/PDE pathway in CSE-/- mice, resulting in a significant reduction in the relaxant response to the sGC redox-dependent stimulator riociguat. However, the response to the sGC redox-independent activator cinaciguat remains unaltered.
PHARMACOLOGICAL RESEARCH
(2023)
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
Biochemistry & Molecular Biology
Alberto Fernando O. Justo, Mariana G. de Oliveira, Fabiano B. Calmasini, Eduardo C. Alexandre, Gabriela Maria Bertollotto, Felipe Fernandes Jacintho, Edson Antunes, Fabiola Z. Monica
Summary: Vascular aging can lead to changes in the structure and function of the iliac arteries, which may contribute to the development of lower urinary tract disorders. The study showed that aged rats had impaired responses to nitric oxide and cGMP, but preserved response to sGC activator.
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2021)
Article
Biology
Jose Britto-Junior, Felipe Fernandes Jacintho, Rafael Campos, David Halen Araujo Pinheiro, Guilherme M. Figueiredo Murari, Valeria B. de Souza, Andre A. Schenka, Fabiola Z. Monica, Ronilson Agnaldo Moreno, Edson Antunes, Gilberto De Nucci
Summary: The study aimed to identify the mediator(s) responsible for the EFS-induced contractions of Chelonoidis carbonaria aortic rings. The results indicate that catecholamines released by endothelium regulate the EFS-induced contractions, possibly constituting a suitable mechanism by which reptiles modulate specific organ blood flow distribution.
Article
Biochemistry & Molecular Biology
Vanessa Aline Bernusso, Karla P. Vieira, Adriana S. S. Duarte, Caroline Honaiser Lescano, Fabiola Zakia Monica, Cristina Pontes Vicente, Erich Vinicius De Paula, Sara Teresinha Olalla Saad, Mariana Lazarini
Summary: The RhoGAP protein ARHGAP21 plays a critical role in megakaryocytic differentiation and platelet function by regulating cytoskeletal rearrangement. Silencing of ARHGAP21 affects microtubule stability and cell spreading, while haploinsufficiency of Arhgap21 leads to enhanced platelet activation and thrombus formation. These findings suggest that ARHGAP21 may be a key protein in the control of platelet production and function.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Gabriela Reolon Passos, Ana Carolina Ghezzi, Edson Antunes, Mariana Goncalves de Oliveira, Fabiola Zakia Monica
Summary: Lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) are highly prevalent worldwide, especially in patients with vascular-related disorders or in the ageing population. Obesity is a significant risk factor for developing LUTS-BPH, with obese men being more likely to develop it. Adipose tissues surrounding the prostate gland release various mediators that can interfere with prostate growth.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Carmem Peres Valgas da Silva, Fabiano Calmasini, Eduardo Costa Alexandre, Helena Fonseca Raposo, Maria Andreia Delbin, Fabiola Zakia Monica, Angelina Zanesco
Summary: The study showed that mirabegron treatment significantly increased energy expenditure in obese mice, improved obesity symptoms, and reduced circulating levels of free fatty acids, glycerol, insulin, inflammatory factors, etc. Additionally, mirabegron may also reverse lipid deposits in the liver and brown adipose tissue.
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
(2021)
Article
Medicine, Research & Experimental
Jose Britto-Junior, Weverton C. Coelho-Silva, Guilherme Figueiredo Murari, Charles Elliot Serpellone Nash, Fabiola Z. Monica, Edson Antunes, Gilberto De Nucci
Summary: This study revealed that 6-nitrodopamine (6-ND) is released by human umbilical cord vessels (HUCV) and acts as a selective dopamine D2-receptor antagonist in this tissue. This represents a novel mechanism by which NO may modulate vascular reactivity independently of cGMP production.
Article
Pharmacology & Pharmacy
Jose Britto-Junior, Andre Ribeiro, Luiz Ximenes, Antonio Tiago Lima, Felipe Fernandes Jacintho, Adriano Fregonesi, Fabiola Z. Monica, Edson Antunes, Gilberto De Nucci
Summary: The study found that alpha(1)-adrenergic receptor antagonists act as 6-ND receptor antagonists in the rat isolated epididymal vas deferens, suggesting that many actions attributed to noradrenaline may actually be due to 6-ND antagonism. This research provides the possibility of a common mechanism of therapeutic action for tricyclic antidepressants and alpha(1)-adrenergic receptor antagonists in the treatment of premature ejaculation, through the blockade of 6-ND receptors.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jose Britto-Junior, Luiz Ximenes, Andre Ribeiro, Adriano Fregonesi, Rafael Campos, Luiz Ricardo de Almeida Kiguti, Fabiola Z. Monica, Edson Antunes, Gilberto De Nucci
Summary: 6-ND is released from rat isolated vas deferens, and its effect on tissue contractility is modulated by various pharmacological agents. SCH-23390 causes a leftward shift in the concentration-response curve to 6-ND, while haloperidol and sonepiprazole induce rightward shifts in dopamine concentration-response curves without affecting 6-ND responses. Tricyclic compounds like desipramine, clomipramine, amitriptyline, cyclobenzaprine, and carbamazepine act as selective 6-ND receptor antagonists.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Akila L. Oliveira, Mariana G. de Oliveira, Matheus L. Medeiros, Fabiola Z. Monica, Edson Antunes
Summary: The study revealed that MGO intake could lead to bladder dysfunction, but this could be reversed by metformin. Mice in the MGO group showed increased basal pressure and non-voiding contractions frequency in the bladder, as well as reduced voiding efficiency, all of which were normalized with metformin treatment.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Immunology
Matheus L. Medeiros, Akila L. Oliveira, Mariana G. de Oliveira, Fabiola Z. Monica, Edson Antunes
Summary: The intake of MGO exacerbates LPS-induced acute lung injury, leading to excessive inflammation and increased oxidative stress. However, metformin can mitigate these adverse effects and offer a potential therapeutic option.
JOURNAL OF INFLAMMATION RESEARCH
(2021)
Article
Hematology
Guilherme Ruiz Leonardi, Caroline Honaiser Lescano, Jose Luiz Costa, Bruna Mazetto, Fernanda Andrade Orsi, Fabiola Zakia Monica
Summary: Platelet reactivity is significantly increased in patients with thrombotic antiphospholipid syndrome (t-PAPS), which may be related to the overexpression of P2Y(12) receptor and the lower levels of cAMP and cGMP.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Physiology
Akila L. Oliveira, Matheus L. Medeiros, Mariana G. de Oliveira, Caio Jordao Teixeira, Fabiola Z. Monica, Edson Antunes
Summary: This study found that MGO can cause bladder overactivity, and its mechanism is related to the activation of the AGE-RAGE-ROS signaling cascade and Rho kinase. Accumulation of MGO leads to an increase in AGEs levels, which in turn activates the RAGE-ROS signaling pathway, ultimately leading to bladder overactivity.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Andrology
Gabriela Reolon Passos, Guilherme Ruiz Leonardi, Mariana Goncalves de Oliveira, Erick de Toledo Gomes, Ana Carolina Ghezzi, Edson Antunes, Fernanda Andrade Orsi, Jose Luiz da Costa, Fabiola Zakia Monica
Summary: This study aimed to assess the effects of serum obtained from unvaccinated men with severe COVID-19 on isolated corpus cavernosum (CC) from mice. The results showed that the relaxation responses in CC incubated with COVID-19 serum were significantly reduced compared to the control serum. However, the relaxation induced by a specific activator was unaffected in CC stimulated with the COVID-19 serum. In addition, COVID-19 serum increased the expression of specific genes. These findings suggest that COVID-19 may lead to erectile dysfunction.
Article
Biology
J. Britto-Junior, A. T. Lima, J. S. Santos-Xavier, P. Gonzalez, F. Z. Monica, R. Campos, V. B. de Souza, A. A. Schenka, E. Antunes, G. De Nucci
Summary: This study investigated the release of 6-nitrodopamine in the thoracic aorta and pulmonary artery rings of marmosets. The results showed that 6-nitrodopamine is the major catecholamine released by marmoset vascular tissues. It acts as a potent and selective antagonist of dopamine D2-like receptors and induces vasodilation by releasing NO.
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
(2023)
Article
Physiology
Akila L. Oliveira, Matheus L. Medeiros, Ana Carolina Ghezzi, Gabriel Alonso dos Santos, Glaucia Coelho Mello, Fabiola Z. Monica, Edson Antunes
Summary: High levels of MGO and AGEs, along with activation of the RAGE pathway, contribute to diabetes-associated bladder dysfunction. Treatment with the AGE breaker ALT-711 can reduce MGO levels and improve bladder function in diabetic mice.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)