Ca2+ mishandling and mitochondrial dysfunction: a converging road to prediabetic and diabetic cardiomyopathy

Giusti, C; Palomeque, Julieta; Mattiazzi, Alicia

doi:10.1007/s00424-021-02650-y

Cited by 17 publications

(16 citation statements)

References 311 publications

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“…Furthermore, hyperglycaemia itself may promote the development of AGEs (Advanced Glycated End-Products) stimulating collagen expression and accumulation, leading to myocardial fibrosis with an increase in myocardial stiffness and reduced cardiac compliance [ 28 , 33 , 34 , 35 ]. High glucose levels also cause Ca 2+ mishandling and mitochondrial dysfunction, which may play a crucial role in the earliest stages of DCM [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Improvement of Left Ventricular Global Longitudinal Strain after 6-Month Therapy with GLP-1RAs Semaglutide and Dulaglutide in Type 2 Diabetes Mellitus: A Pilot Study

Basile¹,

Guaricci²,

Piazzolla

et al. 2023

JCM

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(1) Background: Glucagone-Like Peptide-1 Receptor Agonists (GLP-1 RAs) (GLP-1 RAs) are incretine-based medications recommended in the treatment of type 2 Diabetes Mellitus (DM2) with atherosclerotic cardiovascular disease (ASCVD) or high or very high cardiovascular (CV) risk. However, knowledge of the direct mechanism of GLP-1 RAs on cardiac function is modest and not yet fully elucidated. Left ventricular (LV) Global Longitudinal Strain (GLS) with Speckle Tracking Echocardiography (STE) represents an innovative technique for the evaluation of myocardial contractility. (2) Methods: an observational, perspective, monocentric study was conducted in a cohort of 22 consecutive patients with DM2 and ASCVD or high/very high CV risk, enrolled between December 2019 and March 2020 and treated with GLP-1 RAs dulaglutide or semaglutide. The echocardiographic parameters of diastolic and systolic function were recorded at baseline and after six months of treatment. (3) Results: the mean age of the sample was 65 ± 10 years with a prevalence of the male sex (64%). A significant improvement in the LV GLS (mean difference: −1.4 ± 1.1%; p value < 0.001) was observed after six months of treatment with GLP-1 RAs dulaglutide or semaglutide. No relevant changes were seen in the other echocardiographic parameters. (4) Conclusions: six months of treatment with GLP-1 RAs dulaglutide or semaglutide leads to an improvement in the LV GLS in subjects with DM2 with and high/very high risk for ASCVD or with ASCVD. Further studies on larger populations and with a longer follow-up are warranted to confirm these preliminary results.

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Section: Discussionmentioning

confidence: 99%

Improvement of Left Ventricular Global Longitudinal Strain after 6-Month Therapy with GLP-1RAs Semaglutide and Dulaglutide in Type 2 Diabetes Mellitus: A Pilot Study

Basile¹,

Guaricci²,

Piazzolla

et al. 2023

JCM

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“…The regulation of Ca 2+ homeostasis in mitochondria involves the voltage-dependent anion channel (VDAC), mitochondrial Ca 2+ uniporter complex (MCU), and mitochondrial permeability transition pore (mPTP) ( 184 ). The MCU is a large complex comprising various regulatory proteins, including dominant-negative MCUb, EMRE (essential MCU regulator), and the intermembrane space regulators (EF-hand proteins) MICU1, MICU2, and MICU3.…”

Section: Pathways Regulating Ca 2+ -Dependent Cont...mentioning

confidence: 99%

Signaling Pathways Related to Oxidative Stress in Diabetic Cardiomyopathy

Peng

et al. 2022

Front. Endocrinol.

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Diabetes is a chronic metabolic disease that is increasing in prevalence and causes many complications. Diabetic cardiomyopathy (DCM) is a complication of diabetes that is associated with high mortality, but it is not well defined. Nevertheless, it is generally accepted that DCM refers to a clinical disease that occurs in patients with diabetes and involves ventricular dysfunction, in the absence of other cardiovascular diseases, such as coronary atherosclerotic heart disease, hypertension, or valvular heart disease. However, it is currently uncertain whether the pathogenesis of DCM is directly attributable to metabolic dysfunction or secondary to diabetic microangiopathy. Oxidative stress (OS) is considered to be a key component of its pathogenesis. The production of reactive oxygen species (ROS) in cardiomyocytes is a vicious circle, resulting in further production of ROS, mitochondrial DNA damage, lipid peroxidation, and the post-translational modification of proteins, as well as inflammation, cardiac hypertrophy and fibrosis, ultimately leading to cell death and cardiac dysfunction. ROS have been shown to affect various signaling pathways involved in the development of DCM. For instance, OS causes metabolic disorders by affecting the regulation of PPARα, AMPK/mTOR, and SIRT3/FOXO3a. Furthermore, OS participates in inflammation mediated by the NF-κB pathway, NLRP3 inflammasome, and the TLR4 pathway. OS also promotes TGF-β-, Rho-ROCK-, and Notch-mediated cardiac remodeling, and is involved in the regulation of calcium homeostasis, which impairs ATP production and causes ROS overproduction. In this review, we summarize the signaling pathways that link OS to DCM, with the intention of identifying appropriate targets and new antioxidant therapies for DCM.

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“…The hypersensitivity of cardiac myofibrils to Ca 2+ is a principal factor which leads to impaired cardiomyocyte relaxation [ 103 ]. Ca 2+ mishandling in DCM results in depressed contractility, slow relaxation, triggered arrhythmias, and altered cellular processes, such as apoptosis or mitophagy [ 104 ]. Studies have shown that green tea catechins can be used for cardiomyopathy patients with diastolic dysfunction because of their desensitizing effects [ 105 ].…”

Section: Attenuation Of Secondary Mitochondrial Diseases By Catechinsmentioning

confidence: 99%

A Comprehensive Review on Beneficial Effects of Catechins on Secondary Mitochondrial Diseases

Chen

Zhang

Lin

et al. 2022

IJMS

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Mitochondria are the main sites for oxidative phosphorylation and synthesis of adenosine triphosphate in cells, and are known as cellular power factories. The phrase “secondary mitochondrial diseases” essentially refers to any abnormal mitochondrial function other than primary mitochondrial diseases, i.e., the process caused by the genes encoding the electron transport chain (ETC) proteins directly or impacting the production of the machinery needed for ETC. Mitochondrial diseases can cause adenosine triphosphate (ATP) synthesis disorder, an increase in oxygen free radicals, and intracellular redox imbalance. It can also induce apoptosis and, eventually, multi-system damage, which leads to neurodegenerative disease. The catechin compounds rich in tea have attracted much attention due to their effective antioxidant activity. Catechins, especially acetylated catechins such as epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), are able to protect mitochondria from reactive oxygen species. This review focuses on the role of catechins in regulating cell homeostasis, in which catechins act as a free radical scavenger and metal ion chelator, their protective mechanism on mitochondria, and the protective effect of catechins on mitochondrial deoxyribonucleic acid (DNA). This review highlights catechins and their effects on mitochondrial functional metabolic networks: regulating mitochondrial function and biogenesis, improving insulin resistance, regulating intracellular calcium homeostasis, and regulating epigenetic processes. Finally, the indirect beneficial effects of catechins on mitochondrial diseases are also illustrated by the warburg and the apoptosis effect. Some possible mechanisms are shown graphically. In addition, the bioavailability of catechins and peracetylated-catechins, free radical scavenging activity, mitochondrial activation ability of the high-molecular-weight polyphenol, and the mitochondrial activation factor were also discussed.

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Ca2+ mishandling and mitochondrial dysfunction: a converging road to prediabetic and diabetic cardiomyopathy

Cited by 17 publications

References 311 publications

Improvement of Left Ventricular Global Longitudinal Strain after 6-Month Therapy with GLP-1RAs Semaglutide and Dulaglutide in Type 2 Diabetes Mellitus: A Pilot Study

Improvement of Left Ventricular Global Longitudinal Strain after 6-Month Therapy with GLP-1RAs Semaglutide and Dulaglutide in Type 2 Diabetes Mellitus: A Pilot Study

Signaling Pathways Related to Oxidative Stress in Diabetic Cardiomyopathy

A Comprehensive Review on Beneficial Effects of Catechins on Secondary Mitochondrial Diseases

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