scholarly journals Molecular pathogenesis of heart failure in diabetes mellitus – new direction for the therapeutic approach

2020 ◽  
Vol 74 ◽  
pp. 452-463
Author(s):  
Magdalena Łukawska-Tatarczuk ◽  
Beata Mrozikiewicz-Rakowska ◽  
Edward Franek ◽  
Leszek Czupryniak
Keyword(s):  
Heart Failure ◽  
Cardiovascular Diseases ◽  
Diabetic Cardiomyopathy ◽  
Myocardial Dysfunction ◽  
Cardiovascular Complications ◽  
Diabetic Patients ◽  
Therapeutic Implications ◽  
Immune System Dysfunction ◽  
Individualization Of Therapy ◽  
Clinical Pictures

As it has been proven, cardiovascular diseases are several times more common in diabetic patients than in the general population. Despite many studies and hypotheses, is still not explained why this happens. Considering the frequent coexistence of cardiovascular risk factors with diabetes, the identification of diabetic cardiomyopathy as an independent complication is controversial, and diagnosis in clinical practice is rare. Nevertheless, the presence of diabetes significantly worsens the course and prognosis of cardiovascular diseases, and a better understanding of the diabetic component in the development of heart failure seems essential in the search for an effective therapy. The pathogenetic factors of the development of heart failure in diabetes include: metabolic disorders related to hyperglycaemia, lipotoxicity, insulin resistance, oxidative stress, immune system dysfunction, genetic predisposition and epigenetic disorders. The clinical pictures of diabetic cardiomyopathy vary depending on the type of diabetes, and dysfunction includes not only the cells of the myocardium, as well as stromal cells, endothelial and nervous system cells. The long-term and asymptomatic course of this complication and its progressive nature shortening the lives of diabetic patients prompt the search for new diagnostic and therapeutic methods. A better understanding of the molecular basis of myocardial dysfunction in diabetes appears essential in the search. Stopping the “cascade” of pathways responsible for activation of inflammation, fibrosis or apoptosis in individual organs could effectively prevent the development of diabetic complications. The paper presents existing pathogenetic concepts and their therapeutic implications, which may be used in the prevention of cardiovascular complications in diabetes and allow individualization of therapy.

Oxidative stress and diabetic cardiovascular disorders: roles of mitochondria and NADPH oxidaseThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

2010 ◽  
Vol 88 (3) ◽  
pp. 241-248 ◽  
Author(s):  
Garry X. Shen
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Mitochondrial Dysfunction ◽  
Cardiovascular Complications ◽  
Hypoglycemic Agents ◽  
Diabetic Patients ◽  
Plasminogen Activator Inhibitor 1 ◽  
In Cells

Cardiovascular diseases are the predominant cause of death in patients with diabetes mellitus. Underlying mechanism for the susceptibility of diabetic patients to cardiovascular diseases remains unclear. Elevated oxidative stress was detected in diabetic patients and in animal models of diabetes. Hyperglycemia, oxidatively modified atherogenic lipoproteins, and advanced glycation end products are linked to oxidative stress in diabetes. Mitochondria are one of major sources of reactive oxygen species (ROS) in cells. Mitochondrial dysfunction increases electron leak and the generation of ROS from the mitochondrial respiratory chain (MRC). High levels of glucose and lipids impair the activities of MRC complex enzymes. NADPH oxidase (NOX) generates superoxide from NADPH in cells. Increased NOX activity was detected in diabetic patients. Hyperglycemia and hyperlipidemia increased the expression of NOX in vascular endothelial cells. Accumulated lines of evidence indicate that oxidative stress induced by excessive ROS production is linked to many processes associated with diabetic cardiovascular complications. Overproduction of ROS resulting from mitochondrial dysfunction or NOX activation is associated with uncoupling of endothelial nitric oxide synthase, which leads to reduced production of nitric oxide and endothelial-dependent vasodilation. Gene silence or inhibitor of NOX reduced oxidized or glycated LDL-induced expression of plasminogen activator inhibitor-1 in endothelial cells. Statins, hypoglycemic agents, and exercise may reduce oxidative stress in diabetic patients through the reduction of NOX activity or the improvement of mitochondrial function, which may prevent or postpone the development of cardiovascular complications.

Abstract 372: MicroRNA-9 Inhibits Hyperglycemia-induced Cardiac Pyroptosis by Targeting ELAVL1

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Prince Jeyabal ◽  
Rajarajan A Thandavarayan ◽  
Darukeshwara Joladarashi ◽  
Sahana Suresh Babu ◽  
Shashirekha Krishnamurthy ◽  
...  
Keyword(s):  
Heart Failure ◽  
High Glucose ◽  
Cardiac Tissue ◽  
Critical Role ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Therapeutic Implications ◽  
Caspase 1 ◽  
Ventricular Cardiomyocytes ◽  
Nlrp3 Expression

Diabetic cardiomyopathy is a common complication in patients with diabetes and is associated with underlying chronic inflammation and cardiac cell death, subsequently leading to left ventricular dysfunction and heart failure. ELAV-like protein 1 (ELAVL1, mRNA stabilizing protein) and NLRP3 activation (inflammasome complex protein)-mediated IL-1beta synthesis play a critical role in the progression of heart failure. However, ELAVL1 regulation of pyroptosis (caspase-1-mediated programmed apoptosis) and associated IL-1beta release in cardiomyocytes, especially under diabetic condition, remains elusive. Human diabetic, non-diabetic heart tissues, human ventricular cardiomyocytes and rat cardiomyoblasts exposed to high glucose (HG) were used for our studies. Our data demonstrates that human ventricular cardiomyocytes exposed to high glucose condition showed significant increase in ELAVL1 and NLRP3 expression with a concomitant increase in caspase-1 and IL-1 beta expression. Furthermore, human cardiac tissue from diabetic patients showed increased ELAVL1, caspase-1 and NLRP3 expression as compared to non-diabetic hearts. Intriguingly, ELAVL1 knockdown abrogates TNF-α induced canonical pyroptosis via NLRP3, caspase-1 and IL-1beta suppression. Interestingly, miRNA-9 expression significantly reduces in high glucose treated cardiomyocytes and in human diabetic hearts. Bioinformatics analysis and target validation assays showed that miR-9 directly targets ELAVL1. Inhibition of miR-9 up regulates ELAVL1 expression and activates caspase-1. Alternatively, miR-9 mimics attenuate hyperglycemia-induced ELAVL1 and inhibit cardiomyocyte pyroptosis. To our knowledge, this is the first report to demonstrate the role of miR-9/ELAVL1 in hyperglycemia-induced cardiac pyroptosis. Taken together our study highlights the potential therapeutic implications in preventing cardiomyocyte cell loss in human diabetic failing heart.

scholarly journals Diabetic cardiomyopathy

2009 ◽  
Vol 116 (10) ◽  
pp. 741-760 ◽  
Author(s):  
Omar Asghar ◽  
Ahmed Al-Sunni ◽  
Kaivan Khavandi ◽  
Ali Khavandi ◽  
Sarah Withers ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diabetic Cardiomyopathy ◽  
Disease Process ◽  
Molecular Targets ◽  
Clinical Trial Data ◽  
Experimental Models ◽  
Trial Data ◽  
Diabetic Patients ◽  
Cardiac Safety ◽  
Artery Disease

Diabetic cardiomyopathy is a distinct primary disease process, independent of coronary artery disease, which leads to heart failure in diabetic patients. Epidemiological and clinical trial data have confirmed the greater incidence and prevalence of heart failure in diabetes. Novel echocardiographic and MR (magnetic resonance) techniques have enabled a more accurate means of phenotyping diabetic cardiomyopathy. Experimental models of diabetes have provided a range of novel molecular targets for this condition, but none have been substantiated in humans. Similarly, although ultrastructural pathology of the microvessels and cardiomyocytes is well described in animal models, studies in humans are small and limited to light microscopy. With regard to treatment, recent data with thiazoledinediones has generated much controversy in terms of the cardiac safety of both these and other drugs currently in use and under development. Clinical trials are urgently required to establish the efficacy of currently available agents for heart failure, as well as novel therapies in patients specifically with diabetic cardiomyopathy.

scholarly journals Mitochondrial Arrest on the Microtubule Highway—A Feature of Heart Failure and Diabetic Cardiomyopathy?

2021 ◽  
Vol 8 ◽  
Author(s):  
Sarah Kassab ◽  
Zainab Albalawi ◽  
Hussam Daghistani ◽  
Ashraf Kitmitto
Keyword(s):  
Heart Failure ◽  
Diabetic Cardiomyopathy ◽  
Treatment Options ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Key Factors ◽  
Mitochondrial Movement ◽  
Inflammatory Conditions ◽  
Global Pandemic ◽  
Mitochondrial Motility

A pathophysiological consequence of both type 1 and 2 diabetes is remodelling of the myocardium leading to the loss of left ventricular pump function and ultimately heart failure (HF). Abnormal cardiac bioenergetics associated with mitochondrial dysfunction occurs in the early stages of HF. Key factors influencing mitochondrial function are the shape, size and organisation of mitochondria within cardiomyocytes, with reports identifying small, fragmented mitochondria in the myocardium of diabetic patients. Cardiac mitochondria are now known to be dynamic organelles (with various functions beyond energy production); however, the mechanisms that underpin their dynamism are complex and links to motility are yet to be fully understood, particularly within the context of HF. This review will consider how the outer mitochondrial membrane protein Miro1 (Rhot1) mediates mitochondrial movement along microtubules via crosstalk with kinesin motors and explore the evidence for molecular level changes in the setting of diabetic cardiomyopathy. As HF and diabetes are recognised inflammatory conditions, with reports of enhanced activation of the NLRP3 inflammasome, we will also consider evidence linking microtubule organisation, inflammation and the association to mitochondrial motility. Diabetes is a global pandemic but with limited treatment options for diabetic cardiomyopathy, therefore we also discuss potential therapeutic approaches to target the mitochondrial-microtubule-inflammatory axis.

Abstract 358: Hypoxia and Hyperglycemia Induces M 6 A Mrna Methylation in Major Heart Cells

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Rajesh Kumari ◽  
Prabhat Ranjan ◽  
Zainab Suleiman ◽  
Jing Li ◽  
Suresh K Verma
Keyword(s):  
Heart Failure ◽  
Endothelial Cells ◽  
Heart Disease ◽  
Cardiovascular Diseases ◽  
Neonatal Rat ◽  
Diabetic Heart ◽  
Diabetic Patients ◽  
Heart Cells ◽  
Rat Cardiomyocytes ◽  
Mrna Methylation

Background: According to American heart association, over 70 % diabetic patients die from heart and stroke related diseases. The term “diabetic heart diseases” includes coronary heart disease, heart failure and diabetic cardiomyopathy in diabetic patients. Epigenetic and epitranscriptomic modifications play critical roles in progress of diabetic heart disease. Recent evidences indicated that m 6 A methylation involved in ischemic cardiomyopathy. But, the role of m 6 A mRNA methylation in cardiovascular diseases along with diabetic co-morbidity factors has not been studied in details. Thus, here we hypothesize that alterations in m 6 A mRNA methylation under hypoxic and hyperglycemic conditions contributes to severity of ischemic heart disease. Method and Results: To address our hypothesis, we have determined the levels of m 6 A mRNA methylation in NRVM, NRVF and HUVEC, HMVE and mouse primary endothelial cells under hypoxic and hyperglycemic conditions. We also examined the m 6 A levels in mice hearts post 5 days of MI. m 6 A mRNA methylation was significantly upregulated both in human and mouse ischemic hearts. Furthermore, hypoxia and hyperglycemia significantly induced m 6 A methylation in neonatal rat cardiomyocytes, fibroblasts, and mouse primary endothelial cells (isolated from WT and db/db mice). Next, we measured the methylation machinery both at RNA and protein levels. Interestingly, in corroboration with our methylation data, the expression of both m 6 A writers (Mettl3 and WTAP) and Readers (YTHDF2) was significantly increased. To determine the target transcripts which were highly methylated post-ischemia, we performed deep sequencing of methylated RNA after their immunoprecipitation using MeRIP-sequencing protocol. Our MeRIP-seq data has suggested a differentially m 6 A methylated targets both in-vitro and in-vivo ischemic sample. Conclusion: Over all, for the first time our data showed that hypoxia and hyperglycemia alters m 6 A mRNA methylation which may contribute to enhance the severity of cardiovascular diseases under hyperglycemic conditions. Further understanding of the mechanisms, may present a novel approach to potentially regulate m 6 A methylation, which may help in preventing/reducing heart failure in diabetic patients.

scholarly journals Pattern of Cardiovascular Diseases in Diabetic population - a seven year study in a tertiary care hospital of Bangladesh

2020 ◽  
Vol 8 (2) ◽  
pp. 96-101
Author(s):  
SM Rezaul Irfan ◽  
Samira Humaira Habib ◽  
Shabnam Jahan Hoque ◽  
AKM Mohibullah
Keyword(s):  
Heart Failure ◽  
Heart Disease ◽  
Cardiovascular Diseases ◽  
Observational Study ◽  
Vascular Disease ◽  
Peripheral Vascular Disease ◽  
Diabetic Patients ◽  
Peripheral Vascular ◽  
Different Types ◽  
Diabetic Population

Background: Cardiac involvement in diabetes covers a wide spectrum, ranging from asymptomatic silent ischemia to clinically evident heart failure. The total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030. Up to 80% of diabetic patients die of macrovascular complications, including coronary artery disease (CAD), stroke, and peripheral vascular disease (PVD). CVD is the single-most important contributor, and is responsible for 17% of total mortality. Because of the growing numbers of diabetic patients and the increased mortality after their first cardiovascular event, it is critical to identify and treat risk factors early and aggressively in these patients. Methodology: This is a retrospective observational study carried out in the Department of Cardiology BIRDEM General Hospital Dhaka Bangladesh from 2011 to2017. Total 5598 patients who were admitted to the institute between 2011 to 2017 was studied and evaluated to see the pattern of cardiovascular diseases in diabetic population. Results: Among total 5598 patients, 50.02% were male and 49.98% were female. Majority of them were Diabetic and Hypertensive. Most of the patient having cardiovascular disease belongs to age 50-70 years. IHD was found among 1810(32.33%) patients with slightly male predominance. Different types of Cardiomyopathy were found among 330(5.8%) study population. Heart failure of different forms were present among 632 (11.28%) of patients. Different types of Arrhythmia were found among 159 (2.8%) of admitted patient. Rheumatic Vulvular Heart disease were found 64 (1.1%) of individual. Congenital Heart disease were found among 51 with ASD 36 (70.58%) followed by VSD 15 (29.42%) and PAD in 105 (1.8%). Conclusion: This study reflects the higher incidence of Ischemic Heart Disease and higher association of Hypertensive Heart Disease in Diabetic population mostly affecting the 50-70 year age groups. This observational study also shows that the duration of hospital stay has gradually declined over the course of seven years. The incidence of Cardiomyopathy, Peripheral Vascular Disease and Heart Failure could be different in Diabetic population if wide range multicenter prospective approach would have been applied. Bangladesh Crit Care J September 2020; 8(2): 96-101

scholarly journals New glucose-lowering drugs in patients with heart failure

2021 ◽  
Vol 27 (2) ◽  
pp. 60-64
Author(s):  
Plamen Gatzov
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Cardiovascular Diseases ◽  
Population Aging ◽  
Cardiovascular Complications ◽  
Glucose Lowering ◽  
New Class ◽  
Patients With Heart Failure ◽  
Causes Of Mortality ◽  
Positive Effect

The cardiovascular diseases are one of the main causes of mortality in the countries of Europe and North America. The heart failure (HF) and diabetes mellitus (DM) are widely spread diseases that become more frequent with the population aging in those regions. The algorithm of HF treatment in the last two decades includes several new medications. The SGLT-2 inhibitors (dapaglifl ozin, empaglifl ozin and canaglofl ozin) are new class anti diabetic medications which have positive effect on cardiovascular complications in patients with and without DB. The main trials using those medications in this group of patients and the most probable mechanisms, responsible for their effects, are the topic of this review.

SARS-Cov-2 and Associated Heart Failure

2022 ◽  
pp. 159-175
Author(s):  
Abdelmohcine Aimrane ◽  
Bilal El-Mansoury ◽  
Said Sabir ◽  
Soraia El Baz ◽  
Nadia Zouhairi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Diseases ◽  
Arterial Thrombosis ◽  
Inborn Errors Of Metabolism ◽  
Cardiovascular Complications ◽  
Health Concern ◽  
Inborn Errors ◽  
Health Concerns ◽  
Thrombotic Complications ◽  
Large Vessels

The newly emerged pandemic of coronavirus-induced disease of the year 2019 (COVID-19) has become the utmost health concern worldwide. Patients with COVID-19 are highly susceptible to develop hypercoagulable state increasing the risk of causing venous and arterial thrombosis at both small and large vessels. Additionally, in patients showing co-morbidities, for instance patients with inborn errors of metabolism linked to heart failure, the complications and mortalities are even higher than in any other case. In such frail patients already showing health concerns, the COVID-19-induced pneumonia may cause acute or chronic cardiovascular complications. Indeed, several reports of thrombotic complications in association with other complications has been presented, such as large vessels storks, clotting of catheters, and myocardial injury. Nevertheless, knowledge on the COVID-19-associated cardiovascular diseases remains scarce. Thus, in this chapter, the authors represent an overview of the available data on the induced heart failure related to COVID-19.

Specifics of the diagnosis and treatment of diabetic cardiomyopathy

2020 ◽  
pp. 55-62
Author(s):  
Vsevolod Skvortsov ◽  
Anzhela Borisova
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Diabetic Cardiomyopathy ◽  
Severe Heart Failure ◽  
Diagnosis And Treatment ◽  
Shortness Of Breath ◽  
Pathological Changes ◽  
Electrolyte Disorders ◽  
Clinical Pictures

A complex of pathological changes in heart that are caused by metabolic, vascular and electrolyte disorders during diabetes mellitus is called diabetic cardiomyopathy. The clinical pictures of this condition can be diverse — from an asymptomatic course to severe heart failure with shortness of breath, edema, cardialgia, acrocyanosis.

Diabetic cardiomyopathy: mechanisms, diagnosis and treatment

2004 ◽  
Vol 107 (6) ◽  
pp. 539-557 ◽  
Author(s):  
Sajad A. HAYAT ◽  
Billal PATEL ◽  
Rajdeep S. KHATTAR ◽  
Rayaz A. MALIK
Keyword(s):  
Heart Failure ◽  
Diabetic Cardiomyopathy ◽  
Experimental Studies ◽  
Disease Process ◽  
Diagnostic Methods ◽  
Diabetic Patients ◽  
Developing Heart ◽  
Increased Risk ◽  
Distinct Disease ◽  
Artery Disease

Independent of the severity of coronary artery disease, diabetic patients have an increased risk of developing heart failure. This clinical entity has been considered to be a distinct disease process referred to as ‘diabetic cardiomyopathy’. Experimental studies suggest that extensive metabolic perturbations may underlie both functional and structural alterations of the diabetic myocardium. Translational studies are, however, limited and only partly explain why diabetic patients are at increased risk of cardiomyopathy and heart failure. Although a range of diagnostic methods may help to characterize alterations in cardiac function in general, none are specific for the alterations in diabetes. Treatment paradigms are very much limited to interpretation and translation from the results of interventions in non-diabetic patients with heart failure. This suggests that there is an urgent need to conduct pathogenetic, diagnostic and therapeutic studies specifically in diabetic patients with cardiomyopathy to better understand the factors which initiate and progress diabetic cardiomyopathy and to develop more effective treatments.

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