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Pubblicazioni recenti - diabetic cardiomyopathy
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Neonatal Myocardial Infarction in Association with Gestational Diabetes.
Can J Cardiol2021 Apr;():. doi: S0828-282X(21)00211-7.
Aly Safwat, Aguet Julien, Dragulescu Andrea, Grosse-Wortmann Lars,
Abstract
Fetal and neonatal hypertrophic cardiomyopathy is a complication of gestational diabetes and usually follows a benign course. In this report, we present a rare case of a newborn of a diabetic mother with severe ventricular hypertrophy who developed myocardial infarction (MI) confirmed by elevated cardiac enzymes, electrocardiographic changes as well as subendocardial ischemia on CMR imaging. Follow up revealed complete functional myocardial recovery with normalization of ventricular systolic and diastolic functions on serial echocardiograms.
Copyright © 2021. Published by Elsevier Inc.
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A Role of Glucose Overload in Diabetic Cardiomyopathy in Nonhuman Primates.
J Diabetes Res2021 ;2021():9676754. doi: 10.1155/2021/9676754.
Wang Xiu, Jin Shi, Hu Weina,
Abstract
Type 2 diabetes (T2D) plays a major role in the development of heart failure. Patients with T2D have an increased risk to develop HF than healthy subjects, and they always have very poor outcomes and survival rates. However, the underlying mechanisms for this are still unclear. To help develop new therapeutic interventions, well-characterized animal models for preclinical and translational investigations in T2D and HF are urgently needed. Although studies in rodents are more often used, the research findings in rodents have often failed to be translated into humans due to the significant metabolic differences between rodents and humans. Nonhuman primates (NHPs) serve as valuable translational models between basic studies in rodent models and clinical studies in humans. NHPs can recapitulate the natural progress of these diseases in humans and study the underlying mechanism due to their genetic similarity and comparable spontaneous T2D rates to humans. In this review, we discuss the importance of using NHPs models in understanding diabetic cardiomyopathy (DCM) in humans with aspects of correlations between hyperglycemia and cardiac dysfunction progression, glucose overload, and altered glucose metabolism promoting cardiac oxidative stress and mitochondria dysfunction, glucose, and its effect on cardiac resynchronization therapy with defibrillator (CRT-d), the currently available diabetic NHPs models and the limitations involved in the use of NHP models.
Copyright © 2021 Xiu Wang et al.
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Sarcoplasmic reticulum-mitochondria communication; implications for cardiac arrhythmia.
J Mol Cell Cardiol2021 Apr;156():105-113. doi: S0022-2828(21)00078-X.
Hamilton Shanna, Terentyeva Radmila, Clements Richard T, Belevych Andriy E, Terentyev Dmitry,
Abstract
Sudden cardiac death due to ventricular tachyarrhythmias remains the major cause of mortality in the world. Heart failure, diabetic cardiomyopathy, old age-related cardiac dysfunction and inherited disorders are associated with enhanced propensity to malignant cardiac arrhythmias. Both defective mitochondrial function and abnormal intracellular Ca homeostasis have been established as the key contributing factors in the pathophysiology and arrhythmogenesis in these conditions. This article reviews current advances in understanding of bidirectional control of ryanodine receptor-mediated sarcoplasmic reticulum Ca release and mitochondrial function, and how defects in crosstalk between these two organelles increase arrhythmic risk in cardiac disease.
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Data on effect of Sacubitril/valsartan on cardiac Remodelling in diabetic Cardiomyopathy rats.
Data Brief2021 Apr;35():106963. doi: 10.1016/j.dib.2021.106963.
Ai Jiao, Liu Jing, Liu Mao,
Abstract
Diabetic cardiomyopathy (DCM) is one of the most important causes of death in patients with diabetic mellitus. The effect of sacubitril/valsartan (Sac/Val) on cardiac remodeling in DCM remains unclear. The present raw data were analysed to assess the effect of Sac/Val-on cardiac remodeling and explore the mechanisms of Sac/Val-in protecting the myocardium in DCM rats. The data include the left ventricular/body mass index, IL-6 and TNF-? levels in myocardial tissue, the protein expression levels of phos-p38, Col ? and Col ? in myocardial tissue between pre- and post- Sac/Val-treatment in DCM rats. Compared to DCM rats, the degree of fibrosis and the protein expression of phos-p38, Col ? and Col ? reduced after the treatment of Sac/Val. These data may provide useful bases for future clinical research concerning the application of Sac/Val-in patients with DCM.
© 2021 The Author(s). Published by Elsevier Inc.
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Cinacalcet as a surrogate therapy for diabetic cardiomyopathy in rats through AMPK-mediated promotion of mitochondrial and autophagic function.
Toxicol Appl Pharmacol2021 Apr;():115533. doi: S0041-008X(21)00140-X.
Elrashidy Rania A, Ibrahim Samah E,
Abstract
Decreased activity of AMP-activated protein kinase (AMPK) is implicated in the pathogenesis of diabetic cardiomyopathy (DCM). Recent evidence suggests a crosstalk between cinacalcet and AMPK activation. This study investigated the effects of cinacalcet on cardiac remodeling and dysfunction in type 2 diabetic rats (T2DM). High fat diet for 4?weeks combined with single intraperitoneal injection of streptozotocin (30?mg/kg) was used to induce type 2 diabetes in rats. Diabetic rats were either orally treated with vehicle, 5 or 10?mg/kg cinacalcet for 4?weeks. Control rats were fed standard chow diet and intraperitoneally injected with citrate buffer. T2DM rats showed lower body weight (BW), hyperglycemia and dyslipidemia, along with increased heart weight (HW) and HW/BW ratio. Masson's trichrome stained cardiac sections revealed massive fibrosis in T2DM rats. There were increased TGF-? and hydroxyproline levels, coupled with up-regulation of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in hearts of T2DM rats. These alterations were associated with altered redox imbalance and impaired cardiac functions. Decreased phosphorylation of AMPK at threonine172 residue was found in T2DM hearts. Cinacalcet for 4?weeks significantly activated AMPK and alleviated cardiac remodeling and dysfunction in a dose-dependent manner, without affecting blood glucose, serum calcium and phosphorus levels. Cinacalcet increased the mitochondrial DNA content, and expressions of PGC-1?, UCP-3, beclin-1 and LC3-II/LC3-I ratio. Cinacalcet decreased the pro-apoptotic Bax, while increased the anti-apoptotic Bcl-2 in cardiac tissue of T2DM rats. These findings might highlight cinacalcet as an alternative therapy to combat the development and progression of DCM.
Copyright © 2021. Published by Elsevier Inc.
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Dual therapy with an oral non-vitamin K antagonist and a P2Y12 inhibitor vs triple therapy with aspirin, a P2Y12 inhibitor and a vitamin K antagonist for the treatment of diabetes mellitus patients with co-existing atrial fibrillation following percutaneous coronary intervention: A meta-analysis.
Medicine (Baltimore)2021 Apr;100(15):e25546. doi: 10.1097/MD.0000000000025546.
Wang Qiang, Yang Keping,
Abstract
BACKGROUND:
In this analysis, we aimed to compare the efficacy and safety of dual therapy (DT) with a non-vitamin K oral anticoagulant (NOAC) and an adenosine diphosphate receptor antagonist (P2Y12 inhibitor) vs triple therapy (TT) with aspirin, a P2Y12 inhibitor and a vitamin K antagonist for the treatment of diabetes mellitus (DM) patients with co-existing atrial fibrillation (AF) following percutaneous coronary intervention (PCI).
METHODS:
Medical Literature Analysis and Retrieval System Online (MEDLINE), http://www.ClinicalTrials.gov, Excerpta Medical data BASE (EMBASE), Web of Science, Cochrane Central and Google Scholar were the searched databases. Studies that were randomized trials or observational studies comparing DT vs TT for the treatment of DM patients with co-existing AF following PCI were included in this analysis. The adverse cardiovascular outcomes and bleeding events were the endpoints. This meta-analysis was carried out by the RevMan version 5.4 software. Risk ratios (RR) with 95% confidence intervals (CI) were used to represent data and interpret the analysis.
RESULTS:
A total number of 4970 participants were included whereby 2456 participants were assigned to the DT group and 2514 participants were assigned to the TT group. The enrollment period varied from year 2006 to year 2018. Our current results showed that major adverse cardiac events (RR: 1.00, 95% CI: 0.84-1.20; P?=?.98), mortality (RR: 1.08, 95% CI: 0.78-1.48; P?=?.66), myocardial infarction (RR: 1.02, 95% CI: 0.74-1.42; P?=?.90), stroke (RR: 0.94, 95% CI: 0.53-1.67; P?=?.84) and stent thrombosis (RR: 1.09, 95% CI: 0.56-2.10; P?=?.80) were similar with DT versus TT in these patients. However, the risks for total major bleeding (RR: 0.66, 95% CI: 0.54-0.82; P?=?.0001), total minor bleeding (RR: 0.74, 95% CI: 0.64-0.85; P?=?.0001), Thrombolysis in Myocardial Infarction (TIMI) defined major bleeding (RR: 0.58, 95% CI: 0.35-0.95; P?=?.03), TIMI defined minor bleeding (RR: 0.62, 95% CI: 0.42-0.92; P?=?.02), intra-cranial bleeding (RR: 0.34, 95% CI: 0.13-0.95; P?=?.04) and major bleeding defined by the International Society on Thrombosis and Hemostasis (RR: 0.68, 95% CI: 0.51-0.90; P?=?.008) were significantly higher with TT.
CONCLUSIONS:
DT with a NOAC and a P2Y12 inhibitor was associated with significantly less bleeding events without increasing the adverse cardiovascular outcomes when compared to TT with aspirin, a P2Y12 inhibitor and a Vitamin K antagonist for the treatment of DM patients with co-existing AF following PCI. Hence, DT is comparable in efficacy, but safer compared to TT. This interesting hypothesis will have to be confirmed in future studies.
Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.
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Risk factors of in-stent restenosis in patients with diabetes mellitus after percutaneous coronary intervention: A protocol for systematic review and meta-analysis.
Medicine (Baltimore)2021 Apr;100(15):e25484. doi: 10.1097/MD.0000000000025484.
Li Suiping, Luo Chao, Chen Haimei,
Abstract
BACKGROUND:
Percutaneous coronary intervention (PCI) has become one of the effective methods for the treatment of coronary heart disease (CHD). However, it is easy to have in-stent restenosis (ISR), even cardiovascular events after PCI, which affects the therapeutic effects. The incidence of ISR in diabetes mellitus (DM) patients increased by 2 to 4 times. Early identification of the risk factors of ISR in DM patients after PCI may help clinical staff to prevent and intervene as soon as possible, so it is very important to improve the clinical outcomes of DM patients. Although scholars at home and abroad have studied and summarized the risk factors of ISR in DM patients after PCI, the conclusions are different. Therefore, in this study, meta-analysis was used to summarize the risk factors of ISR in DM patients after PCI, and to explore the characteristics of high-risk groups of ISR, thus providing reference for early identification and prevention of ISR.
METHODS:
We will search related literature from PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database. Eligible studies will be screened based on inclusion criteria. Meanwhile, data extraction, risk of bias assessment, publication bias assessment, subgroup analysis, and quality assessment will be performed. Review Manager Version 5.3 software will be applied for data analysis. Each process is independently conducted by 2 researchers. If there is any objection, it will be submitted to a third researcher for resolution.
RESULTS:
We will disseminate the findings of this systematic review and meta-analysis via publications in peer-reviewed journals.
CONCLUSIONS:
The results of this analysis can be used to generate a risk prediction model and provide an intervention strategy for the occurrence of ISR in DM patients after PCI.
OSF REGISTRATION NUMBER:
DOI 10.17605/OSF.IO/WC87Y.
Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.
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Sirtuins: To Be or Not To Be in Diabetic Cardiomyopathy.
Trends Mol Med2021 Apr;():. doi: S1471-4914(21)00088-5.
Palomer Xavier, Aguilar-Recarte David, García Raquel, Nistal J Francisco, Vázquez-Carrera Manuel,
Abstract
Diabetic cardiomyopathy is the leading cause of death among people with diabetes. Despite its severity and poor prognosis, there are currently no approved specific drugs to prevent or even treat diabetic cardiomyopathy. There is a need to understand the pathogenic mechanisms underlying the development of diabetic cardiomyopathy to design new therapeutic strategies. These mechanisms are complex and intricate and include metabolic dysregulation, inflammation, oxidative stress, fibrosis, and apoptosis. Sirtuins, a group of deacetylase enzymes, play an important role in all these processes and are, therefore, potential molecular targets for treating this disease. In this review, we discuss the role of sirtuins in the heart, focusing on their contribution to the pathogenesis of diabetic cardiomyopathy and how their modulation could be therapeutically useful.
Copyright © 2021 Elsevier Ltd. All rights reserved.
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Autophagy in the diabetic heart: A potential pharmacotherapeutic target in diabetic cardiomyopathy.
Ageing Res Rev2021 Apr;68():101338. doi: S1568-1637(21)00085-4.
Dewanjee Saikat, Vallamkondu Jayalakshmi, Kalra Rajkumar Singh, John Albin, Reddy P Hemachandra, Kandimalla Ramesh,
Abstract
Association of diabetes with an elevated risk of cardiac failure has been clinically evident. Diabetes potentiates diastolic and systolic cardiac failure following the myocardial infarction that produces the cardiac muscle-specific microvascular complication, clinically termed as diabetic cardiomyopathy. Elevated susceptibility of diabetic cardiomyopathy is primarily caused by the generation of free radicals in the hyperglycemic milieu, compromising the myocardial contractility and normal cardiac functions with increasing redox insult, impaired mitochondria, damaged organelles, apoptosis, and cardiomyocytes fibrosis. Autophagy is essentially involved in the recycling/clearing the damaged organelles, cytoplasmic contents, and aggregates, which are frequently produced in cardiomyocytes. Although autophagy plays a vital role in maintaining the cellular homeostasis in diligent cardiac tissues, this process is frequently impaired in the diabetic heart. Given its clinical significance, accumulating evidence largely showed the functional aspects of autophagy in diabetic cardiomyopathy, elucidating its intricate protective and pathogenic outcomes. However, etiology and molecular readouts of these contrary autophagy activities in diabetic cardiomyopathy are not yet comprehensively assessed and translated. In this review, we attempted to assess the role of autophagy and its adaptations in the diabetic heart. To delineate the molecular consequences of these events, we provided detailed insights into the autophagy regulation pieces of machinery including the mTOR/AMPK, TFEB/ZNSCAN3, FOXOs, SIRTs, PINK1/Parkin, Nrf2, miRNAs, and others in the diabetic cardiomyopathy. Given the clinical significance of autophagy in the diabetic heart, we further discussed the potential pharmacotherapeutic strategies towards targeting autophagy. Taken together, the present report meticulously assessed autophagy, its adaptations, and molecular regulations in diabetic cardiomyopathy and reviewed the current autophagy-targeting strategies.
Copyright © 2021 Elsevier B.V. All rights reserved.
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Role of dietary modifications in the management of type 2 diabetic complications.
Pharmacol Res2021 Apr;168():105602. doi: S1043-6618(21)00186-9.
Oza Manisha J, Laddha Ankit P, Gaikwad Anil Bhanudas, Mulay Shrikant R, Kulkarni Yogesh A,
Abstract
Diabetes is a chronic metabolic disorder with a high rate of morbidity and mortality. Insufficient insulin secretion and insulin action are two major causes for the development of diabetes, which is characterized by a persistent increase in blood glucose level. Diet and sedentary life style play pivotal role in development of vascular complications in type 2 diabetes. Dietary modification is associated with a reprogramming of nutrient intake, which are proven to be effective for the management of diabetes and associated complications. Dietary modifications modulate various molecular key players linked with the functions of nutrient signalling, regulation of autophagy, and energy metabolism. It activates silent mating type information regulation 2 homolog1 (SIRT1) and AMP-activated protein kinase (AMPK). AMPK mainly acts as an energy sensor and inhibits autophagy repressor Mammalian target of rapamycin (mTOR) under nutritional deprivation. Under calorie restriction (CR), SIRT1 gets activated directly or indirectly and plays a central role in autophagy via the regulation of protein acetylation. Dietary modification is also effective in controlling inflammation and apoptosis by decreasing the level of pro-inflammatory cytokines like nuclear factor kappa- beta (NF-k?), tissue growth factor-beta (TGF-?), tissue necrosis factor-alpha (TNF-?) and interleukin-6 (IL-6). It also improves glucose homeostasis and insulin secretion through beta cell regeneration. This indicates calorie intake plays a crucial role in the pathogenesis of type 2 diabetes-associated complications. The present review, emphasizes the role of dietary modifications in diabetes and associated complications.
Copyright © 2021 Elsevier Ltd. All rights reserved.
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The therapeutic potentials of apelin in obesity-associated diseases.
Mol Cell Endocrinol2021 Apr;529():111278. doi: S0303-7207(21)00122-2.
Castan-Laurell I, Dray C, Valet P,
Abstract
Apelin, a peptide with several active isoforms ranging from 36 to 12 amino acids and its receptor APJ, a G-protein-coupled receptor, are widely distributed. However, apelin has emerged as an adipokine more than fifteen years ago, integrating the field of inter-organs interactions. The apelin/APJ system plays important roles in several physiological functions both in rodent and humans such as fluid homeostasis, cardiovascular physiology, angiogenesis, energy metabolism. Thus the apelin/APJ system has generated great interest as a potential therapeutic target in different pathologies. The present review will consider the effects of apelin in metabolic diseases such as obesity and diabetes with a focus on diabetic cardiomyopathy among the complications associated with diabetes and APJ agonists or antagonists of interest in these diseases.
Copyright © 2021 Elsevier B.V. All rights reserved.
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MiR-20a-5p overexpression prevented diabetic cardiomyopathy via inhibition of cardiomyocyte apoptosis, hypertrophy, fibrosis, and JNK/NF-?B signaling pathway.
J Biochem2021 Apr;():. doi: mvab047.
Liu Xiaoyu, Guo Bingyan, Zhang Wei, Ma Bocong, Li Yongjun,
Abstract
Diabetic cardiomyopathy (DCM) is a common cardiovascular disease. A declined miR-20a-5p was observed in hearts of diabetic mice, while its effect on DCM remains unknown. Herein, we established streptozotocin-induced DCM rat model and high glucose-stimulated H9C2 model of DCM. They then were treated with adenovirus expressing miR-20a-5p to explore the function of miR-20a-5p. ITT and ipGTT assay revealed that miR-20a-5p reduced blood glucose level. Besides, miR-20a-5p improved cardiac dysfunction reflected by reduced HW/BW and LVDP, and increased LVSP and ±LV dp/dt max. MiR-20a-5p prevented cardiomyocyte apoptosis, along with the up-regulated c-caspase-3, bax and down-regulated bcl-2. Moreover, miR-20a-5p alleviated cardiac hypertrophy as the parameters of ANP, BNP and MyHC-? decreased. Also, miR-20a-5p attenuated the cardiac fibrosis demonstrated by decreased TGF-?1, collagen I levels and the inflammatory response manifested by reduced IL-6, TNF-? and IL-1? production. Furthermore, miR-20a-5p prevented JNK phosphorylation and NF-?B p65nuclear translocation. Similarly, the effects of miR-20a-5p on DCM were confirmed in our in vitro experiments. Additionally, ROCK2 is a possible target gene of miR-20a-5p. ROCK2 overexpression reversed the protective effect of miR-20a-5p on DCM. Overall, miR-20a-5p may effectively ameliorate DCM through improving cardiac metabolism, and subsequently inhibiting inflammation, apoptosis, hypertrophy, fibrosis, and JNK/NF-?B pathway via modulating ROCK2.
© The Author(s) 2021. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.
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Adiponectin Modified BMSCs Alleviate Heart Fibrosis via Inhibition TGF-beta1/Smad in Diabetic Rats.
Front Cell Dev Biol2021 ;9():644160. doi: 10.3389/fcell.2021.644160.
Meng Ke, Cai Huabo, Cai Simin, Hong Yucai, Zhang Xiaoming,
Abstract
Accumulating evidence suggested that bone marrow mesenchymal stem cells (BMSCs) have therapeutic potential for diabetes and heart diseases. However, the effects of BMSC on reducing myocardial fibrosis need to be optimized. This study aimed to investigate the mechanism of adiponectin (APN) modified BMSCs on myocardial fibrosis in diabetic model and . The high-fat diet combined with streptozotocin (STZ) injection were used to induced diabetic rat model. H9c2 cells were cultured under a high glucose medium as model. The BMSCs were modified by APN plasmid or APN small interfering RNA (siRNA), then transplanted to the diabetic rats by a single tail-vein injection, or co-cultured with H9c2 cells. We demonstrated that diabetic rats showed typical diabetic symptoms, such as decreased cardiac function, accumulation of pathological lesions and collagen expression. However, these impairments were significantly prevented by the APN modified BMSCs treatment while no effects on APN siRNA modified BMSCs treated diabetic rats. Moreover, we confirmed that APN modified BMSCs could attenuate the expression of TGF-beta1/smad to suppress the myocardial fibrosis in the diabetic rats and high glucose induced H9c2 cells. The present results for the first time showed that APN modified BMSCs exerted protection on cardiac fibrosis via inhibiting TGF-beta1/smad signal pathway in diabetic rats. Our findings suggested that APN modified BMSCs might be a novel and optimal therapy for the diabetic cardiomyopathy in future.
Copyright © 2021 Meng, Cai, Cai, Hong and Zhang.
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Quality Matters? The Involvement of Mitochondrial Quality Control in Cardiovascular Disease.
Front Cell Dev Biol2021 ;9():636295. doi: 10.3389/fcell.2021.636295.
Lin Kai-Lieh, Chen Shang-Der, Lin Kai-Jung, Liou Chia-Wei, Chuang Yao-Chung, Wang Pei-Wen, Chuang Jiin-Haur, Lin Tsu-Kung,
Abstract
Cardiovascular diseases are one of the leading causes of death and global health problems worldwide. Multiple factors are known to affect the cardiovascular system from lifestyles, genes, underlying comorbidities, and age. Requiring high workload, metabolism of the heart is largely dependent on continuous power supply via mitochondria through effective oxidative respiration. Mitochondria not only serve as cellular power plants, but are also involved in many critical cellular processes, including the generation of intracellular reactive oxygen species (ROS) and regulating cellular survival. To cope with environmental stress, mitochondrial function has been suggested to be essential during bioenergetics adaptation resulting in cardiac pathological remodeling. Thus, mitochondrial dysfunction has been advocated in various aspects of cardiovascular pathology including the response to ischemia/reperfusion (I/R) injury, hypertension (HTN), and cardiovascular complications related to type 2 diabetes mellitus (DM). Therefore, mitochondrial homeostasis through mitochondrial dynamics and quality control is pivotal in the maintenance of cardiac health. Impairment of the segregation of damaged components and degradation of unhealthy mitochondria through autophagic mechanisms may play a crucial role in the pathogenesis of various cardiac disorders. This article provides in-depth understanding of the current literature regarding mitochondrial remodeling and dynamics in cardiovascular diseases.
Copyright © 2021 Lin, Chen, Lin, Liou, Chuang, Wang, Chuang and Lin.
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FoxO1 inhibition alleviates type 2 diabetes-related diastolic dysfunction by increasing myocardial pyruvate dehydrogenase activity.
Cell Rep2021 Apr;35(1):108935. doi: S2211-1247(21)00249-7.
Gopal Keshav, Al Batran Rami, Altamimi Tariq R, Greenwell Amanda A, Saed Christina T, Tabatabaei Dakhili Seyed Amirhossein, Dimaano M Toni E, Zhang Yongneng, Eaton Farah, Sutendra Gopinath, Ussher John R,
Abstract
Type 2 diabetes (T2D) increases the risk for diabetic cardiomyopathy and is characterized by diastolic dysfunction. Myocardial forkhead box O1 (FoxO1) activity is enhanced in T2D and upregulates pyruvate dehydrogenase (PDH) kinase 4 expression, which inhibits PDH activity, the rate-limiting enzyme of glucose oxidation. Because low glucose oxidation promotes cardiac inefficiency, we hypothesize that FoxO1 inhibition mitigates diabetic cardiomyopathy by stimulating PDH activity. Tissue Doppler echocardiography demonstrates improved diastolic function, whereas myocardial PDH activity is increased in cardiac-specific FoxO1-deficient mice subjected to experimental T2D. Pharmacological inhibition of FoxO1 with AS1842856 increases glucose oxidation rates in isolated hearts from diabetic C57BL/6J mice while improving diastolic function. However, AS1842856 treatment fails to improve diastolic function in diabetic mice with a cardiac-specific FoxO1 or PDH deficiency. Our work defines a fundamental mechanism by which FoxO1 inhibition improves diastolic dysfunction, suggesting that it may be an approach to alleviate diabetic cardiomyopathy.
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
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Heart Failure And Diabetes: Perspective Of A Dangerous Association.
Curr Hypertens Rev2021 Apr;():. doi: 10.2174/1573402117666210406111927.
Favaloro Liliana Ehtel, Ratto Roxana Daniela, Musso Carla,
Abstract
The relationship between diabetes and risk of heart failure has been described in previous trials, releasing the importance of the hyperglycemic state that added to other risk factors, favors the development of coronary heart disease. The mechanism by which in the absence of hypertension, obesity and/or dyslipidemia, diabetic patients develop cardiomyopathyhas been less studied. Recently, the Sodium Glucose Co-transporter type 2 inhibitors (SGLT2 inhibitors) used for the treatment of heart failure patients with or without diabetes has been a breakthrough in the field of medicine. This review describes the established pathophysiology of diabetic cardiomyopathy and SGLT2 inhibitors, their mechanisms of action, and benefits in this group of patients.
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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Cardioprotective effects of Fenugreek () seed extract in streptozotocin induced diabetic rats.
J Cardiovasc Thorac Res2021 ;13(1):28-36. doi: 10.34172/jcvtr.2021.01.
Bafadam Soleyman, Mahmoudabady Maryam, Niazmand Saeed, Rezaee Seyed Abdolrahim, Soukhtanloo Mohammad,
Abstract
Inadequate control of diabetes mellitus (DM) leads to considerable cardiovascular implications like diabetic cardiomyopathy (DCM). Cardiomyocyte apoptosis is one of the main mechanisms of DCM pathogenesis associated with hyperglycemia, oxidative stress, inflammation, hyperlipidemia and several other factors. (Fenugreek) has been long used as a traditional medicine and has many therapeutic effects, including anti-diabetic, anti-hyperlipidemia, anti-inflammatory and anti-oxidant properties. The current study aimed to investigate cardioprotective effects of fenugreek seed on diabetic rats. Diabetes was induced in forty-two male rats by injection of streptozotocin (STZ) (60 mg/ kg). Diabetic animals were treated with three different doses of fenugreek seed extract (50, 100 and 200 mg/kg) or metformin (300 mg/kg) for six weeks by gavage. Nondiabetic rats served as controls. Glucose, cholesterol, and triglycerides levels were measured in the blood samples, and oxidative stress markers as well as gene expression of , and were assessed in the cardiac tissues of the experimental groups. Diabetic rats exhibited increased serum glucose, cholesterol and triglycerides levels, elevated markers of oxidative stress thiobarbituric acid-reacting substances (TBARS) levels , total thiol groups (SH), catalase (CAT) and superoxide dismutase (SOD) activity, and enhanced apoptosis cell death (ratio of Bax/Bcl2). Fenugreek seed extract considerably improved metabolism abnormalities, attenuated oxidative stress and diminished apoptosis index. Our study suggests that fenugreek seed may protect the cardiac structure in STZ-induced diabetic rats by attenuating oxidative stress and apoptosis.
© 2021 The Author(s).
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Vildagliptin Attenuates Myocardial Dysfunction and Restores Autophagy via miR-21/SPRY1/ERK in Diabetic Mice Heart.
Front Pharmacol2021 ;12():634365. doi: 10.3389/fphar.2021.634365.
Li Xiaochen, Meng Cheng, Han Fei, Yang Juhong, Wang Jingyu, Zhu Yanjuan, Cui Xiao, Zuo Minxia, Xu Jie, Chang Baocheng,
Abstract
Vildagliptin (vild) improves diastolic dysfunction and is associated with a lower relative risk of major adverse cardiovascular events in younger patients. The present study aimed to evaluate whether vild prevents the development of diabetic cardiomyopathy in type 2 diabetic mice and identify its underlying mechanisms. Type 2 diabetic mouse model was generated using wild-type (WT) (C57BL/6J) and miR-21 knockout mice by treatment with HFD/STZ. Cardiomyocyte-specific miR-21 overexpression was achieved using adeno-associated virus 9. Echocardiography was used to evaluate cardiac function in mice. Morphology, autophagy, and proteins levels in related pathway were analyzed. qRT-PCR was used to detect miR-21. Rat cardiac myoblast cell line (H9c2) cells were transfected with miR-21 mimics and inhibitor to explore the related mechanisms of miR-21 in diabetic cardiomyopathy. Vild restored autophagy and alleviated fibrosis, thereby enhancing cardiac function in DM mice. In addition, miR-21 levels were increased under high glucose conditions. miR-21 knockout DM mice with miR-21 knockout had reduced cardiac hypertrophy and cardiac dysfunction compared to WT DM mice. Overexpression of miR-21 aggravated fibrosis, reduced autophagy, and attenuated the protective effect of vild on cardiac function. In high-glucose-treated H9c2 cells, the downstream effectors of sprouty homolog 1 (SPRY1) including extracellular signal-regulated kinases (ERK) and mammalian target of rapamycin showed significant changes following transfection with miR-21 mimics or inhibitor. The results of our study indicate that vild prevents DCM by restoring autophagy through the miR-21/SPRY1/ERK/mTOR pathway. Therefore, miR-21 is a target in the development of DCM, and vild demonstrates significant potential for clinical application in prevention of DCM.
Copyright © 2021 Li, Meng, Han, Yang, Wang, Zhu, Cui, Zuo, Xu and Chang.
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Epidemiology, Pathophysiology, Diagnosis and Treatment of Heart Failure in Diabetes.
Diabetes Metab J2021 Mar;45(2):146-157. doi: 10.4093/dmj.2020.0282.
Park Jin Joo,
Abstract
The cardiovascular disease continuum begins with risk factors such as diabetes mellitus (DM), progresses to vasculopathy and myocardial dysfunction, and finally ends with cardiovascular death. Diabetes is associated with a 2- to 4-fold increased risk for heart failure (HF). Moreover, HF patients with DM have a worse prognosis than those without DM. Diabetes can cause myocardial ischemia via micro- and macrovasculopathy and can directly exert deleterious effects on the myocardium. Hyperglycemia, hyperinsulinemia, and insulin resistance can cause alterations in vascular homeostasis. Then, reduced nitric oxide and increased reactive oxygen species levels favor inflammation leading to atherothrombotic progression and myocardial dysfunction. The classification, diagnosis, and treatment of HF for a patient with and without DM remain the same. Until now, drugs targeting neurohumoral and metabolic pathways improved mortality and morbidity in HF with reduced ejection fraction (HFrEF). Therefore, all HFrEF patients should receive guideline-directed medical therapy. By contrast, drugs modulating neurohumoral activity did not improve survival in HF with preserved ejection fraction (HFpEF) patients. Trials investigating whether sodium-glucose cotransporter-2 inhibitors are effective in HFpEF are on-going. This review will summarize the epidemiology, pathophysiology, and treatment of HF in diabetes.
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Application of Animal Models in Diabetic Cardiomyopathy.
Diabetes Metab J2021 Mar;45(2):129-145. doi: 10.4093/dmj.2020.0285.
Lee Wang-Soo, Kim Jaetaek,
Abstract
Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a well-known risk factor for heart failure in the form of diabetic cardiomyopathy (DiaCM). Currently, DiaCM is defined as myocardial dysfunction in patients with DM in the absence of coronary artery disease and hypertension. The underlying pathomechanism of DiaCM is partially understood, but accumulating evidence suggests that metabolic derangements, oxidative stress, increased myocardial fibrosis and hypertrophy, inflammation, enhanced apoptosis, impaired intracellular calcium handling, activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, and dysregulation of microRNAs, among other factors, are involved. Numerous animal models have been used to investigate the pathomechanisms of DiaCM. Despite some limitations, animal models for DiaCM have greatly advanced our understanding of pathomechanisms and have helped in the development of successful disease management strategies. In this review, we summarize the current pathomechanisms of DiaCM and provide animal models for DiaCM according to its pathomechanisms, which may contribute to broadening our understanding of the underlying mechanisms and facilitating the identification of possible new therapeutic targets.
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