MicroRNAs: A critical regulator and a promising therapeutic and diagnostic molecule for diabetic cardiomyopathy

2021 ◽  
Vol 21 ◽  
Author(s):  
Priyanka Mathur ◽  
Vibha Rani
Keyword(s):  
Heart Failure ◽  
Diabetic Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Diabetic Patients ◽  
Chronic Hyperglycemia ◽  
Life Threatening ◽  
Diabetic Population ◽  
Artery Disease

: Risk of heart failure is 2-5 times higher in diabetic patients as compared to non-diabetic patients with similar comorbidities. Recent reports suggest that nearly half of the diabetic population remains undiagnosed making diabetic cardiomyopathy (DCM) a clinically relevant entity. In myocardium, chronic hyperglycemia elicits structural and functional abnormalities characterized by ventricular dilation, diastolic dysfunction, fibrosis, and hypertrophy leading to heart failure. Since diabetes is a multifactorial heterogeneous metabolic disorder which cannot be diagnosed or controlled along with coronary artery disease or hypertension, there is an urgent need to understand the underlying molecular mechanisms that leads to DCM and identify potential therapeutic targets. Small non-coding RNAs in particular microRNAs (miRNAs) have emerged as key regulators for several life threatening diseases including DCM. Recent studies have reported that miRNAs not only regulates the fundamental mechanisms of DCM such as insulin resistance, MAPK pathway, PI3K-AkT pathway, oxidative stress, inflammatory signaling but also possesses potential to be a therapeutic or diagnostic target. This review examines the role of critical miRNAs in the onset and pathogenesis of DCM which also depicts high potential as therapeutic and diagnostic in preclinical studies. Further, it highlights the completed and on-going clinical trials going around the globe for diabetes and miRNAs to provide a prospective about the upcoming miRNA therapeutics.

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 Molecular Mechanisms and Epigenetic Regulation in Diabetic Cardiomyopathy

2021 ◽  
Vol 8 ◽  
Author(s):  
Anupam Mittal ◽  
Rajni Garg ◽  
Ajay Bahl ◽  
Madhu Khullar
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Cardiac Metabolism ◽  
Molecular Pathways ◽  
Myocardial Apoptosis ◽  
Epigenetic Modifiers ◽  
Artery Disease ◽  
And Function ◽  
Lifestyle Disease

Diabetes mellitus (DM) is an important lifestyle disease. Type 2 diabetes is one of the prime contributors to cardiovascular diseases (CVD) and diabetic cardiomyopathy (DbCM) and leads to increased morbidity and mortality in patients with DM. DbCM is a typical cardiac disease, characterized by cardiac remodeling in the presence of DM and in the absence of other comorbidities such as hypertension, valvular diseases, and coronary artery disease. DbCM is associated with defective cardiac metabolism, altered mitochondrial structure and function, and other physiological and pathophysiological signaling mechanisms such as oxidative stress, inflammation, myocardial apoptosis, and autophagy. Epigenetic modifiers are crucial players in the pathogenesis of DbCM. Thus, it is important to explore the role of epigenetic modifiers or modifications in regulating molecular pathways associated with DbCM. In this review, we have discussed the role of various epigenetic mechanisms such as histone modifications (acetylation and methylation), DNA methylation and non-coding RNAs in modulating molecular pathways involved in the pathophysiology of the DbCM.

scholarly journals Contribution of Impaired Insulin Signaling to the Pathogenesis of Diabetic Cardiomyopathy

2019 ◽  
Vol 20 (11) ◽  
pp. 2833 ◽  
Author(s):  
Mònica Zamora ◽  
Josep A. Villena
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Insulin Signaling ◽  
Renin Angiotensin System ◽  
Diabetic Patients ◽  
Cardiovascular Risks ◽  
Insulin Resistant ◽  
Pathogenic Factors ◽  
Diabetic Population ◽  
Metabolic Inflexibility ◽  
Artery Disease

Diabetic cardiomyopathy (DCM) has emerged as a relevant cause of heart failure among the diabetic population. Defined as a cardiac dysfunction that develops in diabetic patients independently of other major cardiovascular risks factors, such as high blood pressure and coronary artery disease, the underlying cause of DCMremains to be unveiled. Several pathogenic factors, including glucose and lipid toxicity, mitochondrial dysfunction, increased oxidative stress, sustained activation of the renin-angiotensin system (RAS) or altered calcium homeostasis, have been shown to contribute to the structural and functional alterations that characterize diabetic hearts. However, all these pathogenic mechanisms appear to stem from the metabolic inflexibility imposed by insulin resistance or lack of insulin signaling. This results in absolute reliance on fatty acids for the synthesis of ATP and impairment of glucose oxidation. Glucose is then rerouted to other metabolic pathways, with harmful effects on cardiomyocyte function. Here, we discuss the role that impaired cardiac insulin signaling in diabetic or insulin-resistant individuals plays in the onset and progression of DCM.

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.

scholarly journals Growth Factor Deregulation and Emerging Role of Phosphatases in Diabetic Peripheral Artery Disease

2021 ◽  
Vol 7 ◽  
Author(s):  
Clément Mercier ◽  
Marina Rousseau ◽  
Pedro Geraldes
Keyword(s):  
Growth Factor ◽  
Peripheral Artery Disease ◽  
Molecular Mechanisms ◽  
Diabetic Patients ◽  
Peripheral Artery ◽  
Protein Tyrosine ◽  
Collateral Arteries ◽  
Increased Risk ◽  
Artery Disease

Peripheral artery disease is caused by atherosclerosis of lower extremity arteries leading to the loss of blood perfusion and subsequent critical ischemia. The presence of diabetes mellitus is an important risk factor that greatly increases the incidence, the progression and the severity of the disease. In addition to accelerated disease progression, diabetic patients are also more susceptible to develop serious impairment of their walking abilities through an increased risk of lower limb amputation. Hyperglycemia is known to alter the physiological development of collateral arteries in response to ischemia. Deregulation in the production of several critical pro-angiogenic factors has been reported in diabetes along with vascular cell unresponsiveness in initiating angiogenic processes. Among the multiple molecular mechanisms involved in the angiogenic response, protein tyrosine phosphatases are potent regulators by dephosphorylating pro-angiogenic tyrosine kinase receptors. However, evidence has indicated that diabetes-induced deregulation of phosphatases contributes to the progression of several micro and macrovascular complications. This review provides an overview of growth factor alterations in the context of diabetes and peripheral artery disease, as well as a description of the role of phosphatases in the regulation of angiogenic pathways followed by an analysis of the effects of hyperglycemia on the modulation of protein tyrosine phosphatase expression and activity. Knowledge of the role of phosphatases in diabetic peripheral artery disease will help the development of future therapeutics to locally regulate phosphatases and improve angiogenesis.

scholarly journals Clinical Approach to Diabetic Cardiomyopathy: A Review of Human Studies

2018 ◽  
Vol 25 (13) ◽  
pp. 1510-1524 ◽  
Author(s):  
Roberto Tarquini ◽  
Laura Pala ◽  
Simona Brancati ◽  
Giulia Vannini ◽  
Salvatore De Cosmo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Coronary Artery Disease ◽  
Heart Disease ◽  
Coronary Artery ◽  
Diastolic Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Diabetic Population ◽  
Artery Disease

Background: Diabetic Cardiomyopathy (DC) has been defined as a distinct entity characterized by the presence of diastolic or systolic cardiac dysfunction in a diabetic patient in the absence of other causes for Cardiomyopathy, such as coronary artery disease (CAD), hypertension (HTN), or valvular heart disease. Diabetes affects every organ in the body and cardiovascular disease accounts for two-thirds of the mortality in the diabetic population. Diabetes-related heart disease occurs in the form of coronary artery disease (CAD), cardiac autonomic neuropathy or DC. The prevalence of cardiac failure is high in the diabetic population and DC is a common, but underestimated cause of heart failure in diabetes. The strong association between diabetes and heart failure has fueled intense human and animal research aimed at identifying the mechanisms underlying diabetic myocardial disease. Despite significant progress made, the precise pathogenesis of diabetic Cardiomyopathy is yet to be clearly defined. Hyperglycemia, dyslipidemia and inflammation are thought to play key roles in the generation of reactive oxygen or nitrogen species which are in turn involved. Methods: We have reviewed the up-to-date scientific literature addressing these issues. Results: The myocardial interstitium undergoes alterations resulting in abnormal contractile function noted in DC. In the early stages of the disease, diastolic dysfunction is the only abnormality, but systolic dysfunction supervenes in the later stages with impaired left ventricular ejection fraction. Transmitral Doppler echocardiography is usually used to assess diastolic dysfunction, but tissue Doppler Imaging and Cardiac Magnetic Resonance Imaging are being increasingly used for early detection of DC. Diabetic patients with microvascular complications show the strongest association between diabetes and Cardiomyopathy, an association that parallels the duration and severity of hyperglycemia. Conclusion: The management of DC involves improvement in lifestyle, control of glucose and lipid abnormalities, together with treatment of hypertension and CAD, if present.

Poor outcome of diabetic patients with coronary artery disease and coexisting heart failure

2008 ◽  
Vol 7 ◽  
pp. 19-19
Author(s):  
B PONIKOWSKA ◽  
E JANKOWSKA ◽  
K WEGRZYNOWSKATEODORCZYK ◽  
S POWIERZA ◽  
L BORODULINNADZIEJA ◽  
...  
Keyword(s):  
Heart Failure ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Diabetic Patients ◽  
Poor Outcome ◽  
Artery Disease

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

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