Diabetes and Heart Failure

Mehta, Adi; Bhattacharya, Sanjeeb; Estep, Jerry D.; Faiman, Charles

doi:10.1016/j.cger.2020.04.005

Cited by 6 publications

(1 citation statement)

References 46 publications

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“…Previous studies have indicated that long-term diabetes can lead to heart failure. Myocyte hypertrophy, necrosis, programmed cell death, and myocardial fibrosis all participate in this process, [20] although the mechanisms are not fully understood. Myocardial fibrotic remodeling is one of the major causes of diabetes-related myocardial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Activation of Silent Information Regulator 6 Signaling Attenuates Myocardial Fibrosis by Reducing TGFβ1-Smad2/3 Signaling in a Type 2 Diabetic Animal Model

Wang

Dong

et al. 2021

Cardiology Discovery

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Objective:Long-term diabetes can result in ventricular hypertrophic remodeling, tissue fibrosis, myocardial metabolic defection, and eventually, heart failure. Silent information regulator 6 (SIRT6) exerts beneficial effects against cardiovascular diseases. This study is aimed to investigate whether the direct regulation of myocardial SIRT6 signaling affects cardiac performance in the case of diabetes. Meanwhile, we sought to explore the underlying mechanisms.Methods:Sprague Dawley (SD) rats were used in this experiment. Briefly, type 2 diabetic animal model was generated by streptozotocin administration along with feeding a high-fat diet. The SD rats were randomly assigned to non-diabetic group, diabetic group, diabetic injected with empty adenoviral vectors group and diabetic injected with adenoviral vectors expressing SIRT6 group (n = 10, respectively). The animals were kept for another 4 weeks before sacrifice. Cardiac performance was evaluated by echocardiography. Myocardial fibrosis was determined by Masson's trichrome staining. Myocardial SIRT6 signaling and fibrosis related molecules were measured by western blotting.Results:The diabetic myocardium exhibited markedly enhanced TGFβ1-Smad2/3-induced myocardial fibrosis and reduced SIRT6 and AMP-activated protein kinase (AMPK) signaling. After 4 weeks of SIRT6 adenoviral vector infection, myocardial tissues exhibited markedly enhanced SIRT6 and AMPK signaling. Additionally, myocardial fibrosis and TGFβ1-Smad2/3 signaling were both attenuated in the diabetic injected with adenoviral vectors expressing SIRT6 group.Conclusions:SIRT6-AMPK signaling suppressed the progression of tissue fibrosis in diabetes mellitus rats by inhibiting TGFβ1 and its downstream effector Smad2/3. SIRT6 might serve as an alternative therapeutic target for diabetes-related cardiovascular diseases.

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Section: Discussionmentioning

confidence: 99%

Activation of Silent Information Regulator 6 Signaling Attenuates Myocardial Fibrosis by Reducing TGFβ1-Smad2/3 Signaling in a Type 2 Diabetic Animal Model

Wang

Dong

et al. 2021

Cardiology Discovery

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Hyperglycaemia-induced impairment of the autorhythmicity and gap junction activity of mouse embryonic stem cell-derived cardiomyocyte-like cells

Menzele

Aboalgasm

Ballo

et al. 2022

Histochem Cell Biol

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Diabetes mellitus with hyperglycaemia is a major risk factor for malignant cardiac dysrhythmias.However, the underlying mechanisms remain unclear, especially during the embryonic developmental phase of the heart. This study investigated the effect of hyperglycaemia on the pulsatile activity of stem cell-derived cardiomyocytes. Mouse embryonic stem cells (mESCs) were differentiated into cardiac-like cells through embryoid body (EB) formation, in either baseline glucose or high glucose conditions. Action potentials (APs) were recorded using a voltage-sensitive uorescent dye and gap junction activity was evaluated using scrape-loading lucifer yellow dye transfer assay. Molecular components were detected using immunocytochemistry and immunoblot analyses. High glucose decreased the spontaneous beating rate of EBs and shortened the duration of onset of quinidine-induced asystole. Furthermore, it altered AP amplitude, but not AP duration, and had no impact on the expression of the hyperpolarisationactivated cyclic nucleotide-gated isoform 4 (HCN4) channel nor on the EB beating rate response to ivabradine nor isoprenaline. High glucose also decreased both the intercellular spread of lucifer yellow within an EB and the expression of the cardiac gap junction protein connexin 43 as well as upregulated the expression of transforming growth factor beta 1 (TGFβ1) and phosphorylated Smad3. High glucose suppressed the autorhythmicity and gap junction conduction of mESC-derived cardiomyocytes, via mechanisms probably involving TGFβ1/Smad3 signalling. The results allude to glucotoxicity related proarrhythmic effects, with potential clinical implications in foetal diabetic cardiac disease.

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Neurological complications of heart failure

Massaro

2021

Handbook of Clinical Neurology

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Diabetes and Heart Failure

Cited by 6 publications

References 46 publications

Activation of Silent Information Regulator 6 Signaling Attenuates Myocardial Fibrosis by Reducing TGFβ1-Smad2/3 Signaling in a Type 2 Diabetic Animal Model

Activation of Silent Information Regulator 6 Signaling Attenuates Myocardial Fibrosis by Reducing TGFβ1-Smad2/3 Signaling in a Type 2 Diabetic Animal Model

Hyperglycaemia-induced impairment of the autorhythmicity and gap junction activity of mouse embryonic stem cell-derived cardiomyocyte-like cells

Neurological complications of heart failure

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