Citations to this article
Citation Information: JCI Insight. 2018;3(4):e96006. https://doi.org/10.1172/jci.insight.96006.
Abstract
Heart failure with preserved ejection fraction (HFpEF) can arise from cardiac and vascular remodeling processes following long-lasting hypertension. Efficacy of common HF therapeutics is unsatisfactory in HFpEF. Evidence suggests that stimulators of the nitric oxide–sensitive soluble guanylyl cyclase (NOsGC) could be of use here. We aimed to characterize the complex cardiovascular effects of NOsGC stimulation using NO-independent stimulator BAY 41-8543 in a double-transgenic rat (dTGR) model of HFpEF. We show a drastically improved survival rate of treated dTGR. We observed less cardiac fibrosis, macrophage infiltration, and gap junction remodeling in treated dTGR. Microarray analysis revealed that treatment of dTGR corrected the dysregulateion of cardiac genes associated with fibrosis, inflammation, apoptosis, oxidative stress, and ion channel function toward an expression profile similar to healthy controls. Treatment reduced systemic blood pressure levels and improved endothelium-dependent vasorelaxation of resistance vessels. Further comprehensive in vivo phenotyping showed an improved diastolic cardiac function, improved hemodynamics, and less susceptibility to ventricular arrhythmias. Short-term BAY 41-8543 application in isolated untreated transgenic hearts with structural remodeling significantly reduced the occurrence of ventricular arrhythmias, suggesting a direct nongenomic role of NOsGC stimulation on excitation. Thus, NOsGC stimulation was highly effective in improving several HFpEF facets in this animal model, underscoring its potential value for patients.
Authors
Nicola Wilck, Lajos Markó, András Balogh, Kristin Kräker, Florian Herse, Hendrik Bartolomaeus, István A. Szijártó, Maik Gollasch, Nadine Reichhart, Olaf Strauss, Arnd Heuser, Damian Brockschnieder, Axel Kretschmer, Ralf Lesche, Florian Sohler, Johannes-Peter Stasch, Peter Sandner, Friedrich C. Luft, Dominik N. Müller, Ralf Dechend, Nadine Haase
Citations to this article (23)
| Title and authors | Publication | Year |
|---|---|---|
|
Use of Statins in Heart Failure with Preserved Ejection Fraction: Current Evidence and Perspectives
Ovchinnikov A, Potekhina A, Arefieva T, Filatova A, Ageev F, Belyavskiy E |
International journal of molecular sciences | 2024 |
|
sGC stimulator (BAY 41‐8543) combined with PDE9 inhibitor (BAY 73‐6691) reduces renal fibrosis in 5/6 nephrectomized rats
Chen X, Delić D, Liu Y, Cao Y, Zhang Z, Wu H, Gaballa MM, Klein T, Elitok S, Krämer BK, Hocher B |
Basic & Clinical Pharmacology & Toxicology | 2024 |
|
FFAR4 regulates cardiac oxylipin balance to promote inflammation resolution in HFpEF secondary to metabolic syndrome
Naixin Zhang, Katherine Murphy, Brian Harsch, Michael Zhang, Dylan Gyberg, Brandon Wagner, Jenna Mendelson, Michael Patterson, Devin A. Orchard, Chastity Healy, Jesse Williams, Gregory Shearer, Timothy O'Connell |
Journal of lipid research | 2023 |
|
Searching for Effective Treatments in HFpEF: Implications for Modeling the Disease in Rodents.
Jasińska-Stroschein M |
Pharmaceuticals (Basel, Switzerland) | 2023 |
|
Cyclic GMP and PKG Signaling in Heart Failure
G Numata, E Takimoto |
Frontiers in pharmacology | 2022 |
|
Single Donor Infusion of S-Nitroso-Human-Serum-Albumin Attenuates Cardiac Isograft Fibrosis and Preserves Myocardial Micro-RNA-126-3p in a Murine Heterotopic Heart Transplant Model
Anne-Kristin Schaefer, Attila Kiss, André Oszwald, Felix Nagel, Eylem Acar, Arezu Aliabadi-Zuckermann, Matthias Hackl, Andreas Zuckermann, Renate Kain, Andrzej Jakubowski, Peter Ferdinandy, Seth Hallström, Bruno K Podesser |
Transplant international : official journal of the European Society for Organ Transplantation | 2022 |
|
Endothelial Dysfunction in Heart Failure With Preserved Ejection Fraction: What are the Experimental Proofs?
Cornuault L, Rouault P, Duplàa C, Couffinhal T, Renault MA |
Frontiers in physiology | 2022 |
|
Nitric Oxide Signalling in Descending Vasa Recta after Hypoxia/Re-Oxygenation
Xu M, Lichtenberger FB, Erdoǧan C, Lai E, Persson PB, Patzak A, Khedkar PH |
International journal of molecular sciences | 2022 |
|
Bibliometric study of soluble guanylate cyclase stimulators in cardiovascular research based on web of science from 1992 to 2021
Jia XY, Liu YM, Wang YF, An JY, Peng KL, Wang H |
Frontiers in pharmacology | 2022 |
|
From Structural to Functional Hypertension Mediated Target Organ Damage—A Long Way to Heart Failure with Preserved Ejection Fraction
Mancusi C, Lembo M, Manzi MV, Basile C, Fucile I, Morisco C |
Journal of Clinical Medicine | 2022 |
|
Vascular dysfunction in HFpEF: Potential role in the development, maintenance, and progression of the disease
Saavedra-Alvarez A, Pereyra KV, Toledo C, Iturriaga R, Del Rio R |
Frontiers in Cardiovascular Medicine | 2022 |
|
New Opportunities in Heart Failure with Preserved Ejection Fraction: From Bench to Bedside… and Back.
Parra-Lucares A, Romero-Hernández E, Villa E, Weitz-Muñoz S, Vizcarra G, Reyes M, Vergara D, Bustamante S, Llancaqueo M, Toro L |
Biomedicines | 2022 |
|
Changes of Necroptosis in Irbesartan Medicated Cardioprotection in Diabetic Rats
Q Xu, X Tan, W Xian, J Geng, H Li, B Tang, H Zhang, H Wang, Q Gao, P Kang |
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy | 2021 |
|
Resveratrol Ameliorates Cardiac Remodeling in a Murine Model of Heart Failure With Preserved Ejection Fraction
L Zhang, J Chen, L Yan, Q He, H Xie, M Chen |
Frontiers in pharmacology | 2021 |
|
Enhanced Cardiomyocyte Function in Hypertensive Rats With Diastolic Dysfunction and Human Heart Failure Patients After Acute Treatment With Soluble Guanylyl Cyclase (sGC) Activator
D Kolijn, Á Kovács, M Herwig, M Lódi, M Sieme, A Alhaj, P Sandner, Z Papp, PH Reusch, P Haldenwang, I Falcão-Pires, WA Linke, K Jaquet, SV Linthout, A Mügge, C Tschöpe, N Hamdani |
Frontiers in physiology | 2020 |
|
Estrogen Receptor−α Non-Nuclear Signaling Confers Cardioprotection and Is Essential to cGMP-PDE5 Inhibition Efficacy
N Fukuma, E Takimoto, K Ueda, P Liu, M Tajima, Y Otsu, T Kariya, M Harada, H Toko, K Koga, RM Blanton, RH Karas, I Komuro |
JACC: Basic to Translational Science | 2020 |
|
Hemodynamic Effects of a Soluble Guanylate Cyclase Stimulator, Riociguat, and an Activator, Cinaciguat, During NO-Modulation in Healthy Pigs
T Næsheim, OJ How, T Myrmel |
Journal of cardiovascular pharmacology and therapeutics | 2020 |
|
Effects of empagliflozin and target-organ damage in a novel rodent model of heart failure induced by combined hypertension and diabetes
K Kräker, F Herse, M Golic, N Reichhart, S Crespo-Garcia, O Strauß, J Grune, U Kintscher, M Ebrahim, M Bader, N Alenina, A Heuser, FC Luft, DN Müller, R Dechend, N Haase |
Scientific Reports | 2020 |
|
Effects of irbesartan on myocardial injury in diabetic rats: The role of NLRP3/ASC/Caspase-1 pathway
L Rong, S Sun, F Zhu, Q Xu, H Li, Q Gao, W Zhang, B Tang, H Zhang, H Wang, P Kang |
Journal of Renin-Angiotensin-Aldosterone System | 2020 |
|
Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction
D DAmario, S Migliaro, JA Borovac, A Restivo, R Vergallo, M Galli, AM Leone, RA Montone, G Niccoli, N Aspromonte, F Crea |
Frontiers in physiology | 2019 |
|
Inflammatory and Molecular Pathways in Heart Failure—Ischemia, HFpEF and Transthyretin Cardiac Amyloidosis
DM da Silva, H Langer, T Graf |
International journal of molecular sciences | 2019 |
|
Accurate assessment of LV function using the first automated 2D-border detection algorithm for small animals - evaluation and application to models of LV dysfunction
J Grune, D Ritter, K Kräker, K Pappritz, N Beyhoff, T Schütte, C Ott, C John, S van Linthout, C Tschöpe, R Dechend, DN Muller, N Haase, T Grune, U Kintscher, WM Kuebler |
Cardiovascular ultrasound | 2019 |
|
Reactive Oxygen Species: Network Pharmacology and Therapeutic Applications
HH Schmidt, P Ghezzi, A Cuadrado |
2018 |
