ArticleCardiovascular diabetology2015
The soluble guanylate cyclase activator cinaciguat prevents cardiac dysfunction in a rat model of type-1 diabetes mellitus.
Article in Cardiovascular diabetology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 55 citations in OpenAlex.
- Neuroprotective Effect of a Novel Soluble Guanylate Cyclase Activator Runcaciguat in Diabetic and Ischemic Retinopathy.Diabetes · 2025Article
- Inhibiting atrial natriuretic peptide clearance reduces myocardial fibrosis and improves cardiac function in diabetic rats.European heart journal open · 2025Article
- Roles of Empagliflozin in Diabetic Cardiomyopathy: A Review.Current vascular pharmacology · 2025Review
- Role and molecular mechanisms of SGLT2 inhibitors in pathological cardiac remodeling (Review).Molecular medicine reports · 2024Review
- CYB5R3 in type II alveolar epithelial cells protects against lung fibrosis by suppressing TGF-β1 signaling.JCI insight · 2023Article
- Emerging Therapy for Diabetic Cardiomyopathy: From Molecular Mechanism to Clinical Practice.Biomedicines · 2023Review
- Nutraceutical Prevention of Diabetic Complications-Focus on Dicarbonyl and Oxidative Stress.Current issues in molecular biology · 2022Review
- Bibliometric study of soluble guanylate cyclase stimulators in cardiovascular research based on web of science from 1992 to 2021.Frontiers in pharmacology · 2022Article
- A nutraceutical strategy for downregulating TGFβ signalling: prospects for prevention of fibrotic disorders, including post-COVID-19 pulmonary fibrosis.Open heart · 2021Article
- Targeted Delivery of Soluble Guanylate Cyclase (sGC) Activator Cinaciguat to Renal Mesangial Cells via Virus-Mimetic Nanoparticles Potentiates Anti-Fibrotic Effects by cGMP-Mediated Suppression of the TGF-β Pathway.International journal of molecular sciences · 2021Article
- Soluble Guanylate Cyclase Stimulators and Activators.Handbook of experimental pharmacology · 2021Article
- Stimulation of soluble guanylate cyclase improves donor organ function in rat heart transplantation.Scientific reports · 2020Article
- Nitroxyl: A Novel Strategy to Circumvent Diabetes Associated Impairments in Nitric Oxide Signaling.Frontiers in pharmacology · 2020Review
- Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212.Scientific reports · 2019Article
- Selective Heart Irradiation Induces Cardiac Overexpression of the Pro-hypertrophic miR-212.Frontiers in oncology · 2019Article
- Comparison of speckle-tracking echocardiography with invasive hemodynamics for the detection of characteristic cardiac dysfunction in type-1 and type-2 diabetic rat models.Cardiovascular diabetology · 2018Article
- Comparison of the Reverse-Remodeling Effect of Pharmacological Soluble Guanylate Cyclase Activation With Pressure Unloading in Pathological Myocardial Left Ventricular Hypertrophy.Frontiers in physiology · 2018Article
- Pharmacological preconditioning with gemfibrozil preserves cardiac function after heart transplantation.Scientific reports · 2017Article
- Cinaciguat ameliorates glomerular damage by reducing ERK1/2 activity and TGF-ß expression in type-1 diabetic rats.Scientific reports · 2017Article
- Supplementation with Phycocyanobilin, Citrulline, Taurine, and Supranutritional Doses of Folic Acid and Biotin-Potential for Preventing or Slowing the Progression of Diabetic Complications.Healthcare (Basel, Switzerland) · 2017Article
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiabetes mellitus (DM) leads to the development of diabetic cardiomyopathy, which is associated with altered nitric oxide (NO)--soluble guanylate cyclase (sGC)--cyclic guanosine monophosphate (cGMP) signalling. Cardioprotective effects of elevated intracellular cGMP-levels have been described in different heart diseases. In the current study we aimed at investigating the effects of pharmacological activation of sGC in diabetic cardiomyopathy.
methodsType-1 DM was induced in rats by streptozotocin. Animals were treated either with the sGC activator cinaciguat (10 mg/kg/day) or with placebo orally for 8 weeks. Left ventricular (LV) pressure-volume (P-V) analysis was used to assess cardiac performance. Additionally, gene expression (qRT-PCR) and protein expression analysis (western blot) were performed. Cardiac structure, markers of fibrotic remodelling and DNA damage were examined by histology, immunohistochemistry and TUNEL assay, respectively.
resultsDM was associated with deteriorated cGMP signalling in the myocardium (elevated phosphodiesterase-5 expression, lower cGMP-level and impaired PKG activity). Cardiomyocyte hypertrophy, fibrotic remodelling and DNA fragmentation were present in DM that was associated with impaired LV contractility (preload recruitable stroke work (PRSW): 49.5 ± 3.3 vs. 83.0 ± 5.5 mmHg, P < 0.05) and diastolic function (time constant of LV pressure decay (Tau): 17.3 ± 0.8 vs. 10.3 ± 0.3 ms, P < 0.05). Cinaciguat treatment effectively prevented DM related molecular, histological alterations and significantly improved systolic (PRSW: 66.8 ± 3.6 mmHg) and diastolic (Tau: 14.9 ± 0.6 ms) function.
conclusionsCinaciguat prevented structural, molecular alterations and improved cardiac performance of the diabetic heart. Pharmacological activation of sGC might represent a new therapy approach for diabetic cardiomyopathy.
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