Comparison of the reverse-remodeling effect of pharmacological soluble guanylate cyclase activation with pressure unloading in pathological myocardial left ventricular hypertrophy

• Verfasst von: Ruppert, Mihály [VerfasserIn]
• Verfasst von: Korkmaz-İçöz, Sevil [VerfasserIn]
• Verfasst von: Li, Shiliang [VerfasserIn]
• Verfasst von: Brlecic, Paige [VerfasserIn]
• Verfasst von: Veres, Gábor [VerfasserIn]
• Verfasst von: Pleger, Sven Torsten [VerfasserIn]
• Verfasst von: Grabe, Niels [VerfasserIn]
• Verfasst von: Karck, Matthias [VerfasserIn]
• Verfasst von: Szabó, Gábor [VerfasserIn]
• Titel: Comparison of the reverse-remodeling effect of pharmacological soluble guanylate cyclase activation with pressure unloading in pathological myocardial left ventricular hypertrophy
• Verf.angabe: Mihály Ruppert, Sevil Korkmaz-Icöz, Shiliang Li, Paige Brlecic, Balázs Tamás Németh, Attila Oláh, Eszter M. Horváth, Gábor Veres, Sven Pleger, Niels Grabe, Béla Merkely, Matthias Karck, Tamás Radovits and Gábor Szabó
• E-Jahr: 2019
• Jahr: 08 January 2019
• Fussnoten: Gesehen am 03.05.2019
• Titel Quelle: Enthalten in: Frontiers in physiology
• Ort Quelle: Lausanne : Frontiers Research Foundation, 2007
• Jahr Quelle: 2019
• Band/Heft Quelle: 9(2019) Artikel-Nummer 1869, 16 Seiten
• ISSN Quelle: 1664-042X
• DOI: doi:10.3389/fphys.2018.01869
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: cGMP
• Sach-SW: cinaciguat
• Sach-SW: Left ventricular hyperertrophy
• Sach-SW: pressure unloading
• Sach-SW: Reverse remodeling
• K10plus-PPN: 1664577254

Abstract

Background: Pressure unloading induces the regression of left ventricular myocardial hypertrophy (LVH). Recent findings indicate that pharmacological activation of the soluble guanylate cyclase (sGC) - cyclic guanosine monophosphate (cGMP) pathway may also exert reverse-remodeling properties in the myocardium. Therefore, we aimed to investigate the effects of the sGC activator cinaciguat in a rat model of LVH and compare it to the “gold standard” pressure unloading therapy. Methods: Abdominal aortic banding was performed for 6 or 12 weeks. Sham operated animals served as controls. Pressure unloading was induced by removing the aortic constriction after week 6. The animals were treated from week 7 to 12, with 10 mg/kg/day cinaciguat or with placebo p.o., respectively. Cardiac function and morphology were assessed by left ventricular pressure-volume analysis and echocardiography. Additionally, key markers of myocardial hypertrophy, fibrosis, nitro-oxidative stress, apoptosis and cGMP signaling were analyzed. Results: Pressure unloading effectively reversed LVH, decreased collagen accumulation and provided protection against oxidative stress and apoptosis. Regression of LVH was also associated with a full recovery of cardiac function. In contrast, chronic activation of the sGC enzyme by cinaciguat at sustained pressure overload only slightly influenced pre-established hypertrophy. However, it led to increased PKG activity and had a significant impact on interstitial fibrosis, nitro-oxidative stress and apoptosis. Amelioration of the pathological structural alterations prevented the deterioration of LV systolic function (contractility and EF) and improved myocardial stiffness. Conclusion: Our results indicate that both cinaciguat treatment and pressure unloading evoked anti-remodeling effects and improved LV function, however in a differing manners.