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Mechanisms of Diabetic Cardiomyopathy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 December 2024 | Viewed by 899

Special Issue Editor


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Guest Editor
Department of Pharmacology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany
Interests: cardiovascular system; lower urinary tract

Special Issue Information

Dear Colleagues,

When phosphodiesterase type 4 inhibitors and β-adrenoceptor agonists were found to be detrimental in chronic heart failure treatment, new treatments did not become available for a long time. This has changed with the advent of a neprilysin inhibitor/angiotensin receptor antagonist combination and, most recently, SGLT4 inhibitors. These new drug classes have also opened up avenues to more specifically treat cardiomyopathy as it occurs as a consequence of diabetes.

This Special Issue will welcome manuscripts exploring the pathophysiology and treatment of diabetic cardiomyopathy based on applicable cellular models, animal models and human isolated tissues; clinical studies in humans are also welcome if they provide mechanistic insight. Similarly, work on established drugs and drug targets and insight on potential new treatments will be welcome. Studies providing molecular and mechanistic insight will be particularly welcome.

Prof. Dr. Martin Michel
Guest Editor

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Keywords

  • diabetes
  • cardiomyopathy
  • animal models
  • novel treatments
  • pathophyiology
  • SGLT2 inhibitors
  • neprilysin inhibitors

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Published Papers (1 paper)

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Research

20 pages, 6050 KiB  
Article
Sacubitril/Valsartan Combination Partially Improves Cardiac Systolic, but Not Diastolic, Function through β-AR Responsiveness in a Rat Model of Type 2 Diabetes
by Betul R. Erdogan, Zeynep E. Yesilyurt-Dirican, Irem Karaomerlioglu, Ayhanim Elif Muderrisoglu, Kadir Sevim, Martin C. Michel and Ebru Arioglu-Inan
Int. J. Mol. Sci. 2024, 25(19), 10617; https://doi.org/10.3390/ijms251910617 - 2 Oct 2024
Viewed by 684
Abstract
Cardiovascular complications are the major cause of diabetes mellitus-related morbidity and mortality. Increased renin–angiotensin–aldosterone system activity and decreased β-adrenergic receptor (β-AR) responsiveness contribute to diabetic cardiac dysfunction. We evaluated the effect of sacubitril/valsartan (neprilysin inhibitor plus angiotensin receptor antagonist combination) and valsartan treatments [...] Read more.
Cardiovascular complications are the major cause of diabetes mellitus-related morbidity and mortality. Increased renin–angiotensin–aldosterone system activity and decreased β-adrenergic receptor (β-AR) responsiveness contribute to diabetic cardiac dysfunction. We evaluated the effect of sacubitril/valsartan (neprilysin inhibitor plus angiotensin receptor antagonist combination) and valsartan treatments on the diabetic cardiac function through β-AR responsiveness and on protein expression of diastolic components. Six-week-old male Sprague Dawley rats were divided into control, diabetic, sacubitril/valsartan (68 mg/kg)-, and valsartan-treated (31 mg/kg) diabetic groups. Diabetes was induced by a high-fat diet plus low-dose streptozotocin (30 mg/kg, intraperitoneal). After 10 weeks of diabetes, rats were treated for 4 weeks. Systolic/diastolic function was assessed by in vivo echocardiography and pressure–volume loop analysis. β-AR-mediated responsiveness was assessed by in vitro papillary muscle and Langendorff heart experiments. Protein expression of sarcoplasmic reticulum calcium ATPase2a, phospholamban, and phosphorylated phospholamban was determined by Western blot. Sacubitril/valsartan improved ejection fraction and fractional shortening to a similar extent as valsartan alone. None of the treatments affected in vivo diastolic parameters or the expression of related proteins. β1-/β2-AR-mediated responsiveness was partially restored in treated animals. β3-AR-mediated cardiac relaxation (an indicator of diastolic function) responses were comparable among groups. The beneficial effect of sacubitril/valsartan on systolic function may be attributed to improved β1-/β2-AR responsiveness. Full article
(This article belongs to the Special Issue Mechanisms of Diabetic Cardiomyopathy)
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