DOCSLIB.ORG

The Protective Effect of Resveratrol on Diabetic Cardiomyopathy Tugba Karadeniz1 and Muammer Karadeniz2,3*

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Protective Effect of Resveratrol on Diabetic Cardiomyopathy Tugba Karadeniz1 and Muammer Karadeniz2,3* ISSN: 2377-3634 Karadeniz and Karadeniz. Int J Diabetes Clin Res 2018, 5:089 DOI: 10.23937/2377-3634/1410089 Volume 5 | Issue 2 International Journal of Open Access Diabetes and Clinical Research REVIEW ARTICLE The Protective Effect of Resveratrol on Diabetic Cardiomyopathy Tugba Karadeniz1 and Muammer Karadeniz2,3* 1Department of Pathology, Izmir Tepecik Training and Research Hospital, Turkey 2 Check for Department of Internal Medicine, Izmir University, Turkey updates 3Department of Endocrinology, Izmir University, Turkey *Corresponding author: Muammer Karadeniz, MD, Faculty of Medicine, Department of Endocrinology, Izmir University, Karşıyaka, İzmir, Turkey, E-mail: [email protected] potoxicity and mitochondrial dysfunction plays a main Abstract role in the development of cardiomyopathy in diabetic Based on the key role of hyperglycemia-caused oxidative patients [4,5]. stress in the formation of diabetic cardiomyopathy, incre- ased antioxidant process would best restorative approa- The mechanism of diabetic cardiomyopathy are dif- ch for control of diabetic cardiomyopathy. The increased ferent and may related increased oxidative/nitrosative nitrative stress and peroxynitrite, activation of iNOS and TGF-B1 play a crucial role in the pathogenesis of diabetic stress with induced hyperglycemia [6], and activation of cardiomyopathy. Reduction of the expressions of the NOS- its downstream effector pathways (e.g. poly(ADP-ribo- 2 and TGF-B1 appears to be one of the important mechani- se) polymerase (PARP)) [7,8], changes in the composi- sms for resveratrol effect on heart. tion of extracellular matrix with increased myocardial Keywords fibrosis and inflammation [9,10]. Type 2 diabetes, Antioxidant, Hyperglycemia, Redox sta- Hyperglycemia has been shown to inhibit the pro- tus, Cardiomyopathy, Resveratrol survival effect of VEGF, leading to cell apoptosis via tyrosine nitration of PI3Kinase that results in Akt inacti- Introduction vation and increased p38 mitogen-activated protein ki- Coronary artery disease leading to myocardial infar- nase activation in cells [11]. NO, synthesized from L-ar- ction and heart failure is a chronic complication of dia- ginine by 3 NO synthase (NOS) enzymes, is a biological betes [1]. After a myocardial ischemic event, diabetes is mediator with multiple actions [12]. Two constitutively associated with increased adverse outcomes in terms present enzymes are found in neuronal and endothelial of both morbidity and mortality over the short and long cells, respectively; the third form is inducible in many term [2]. cells by endotoxin and cytokines, such as interleukin-1, interferon-γ, and TNF-α [13,14]. Diabetic cardiomyopathy, a disorder of the heart muscle in diabetic patients, is one of the major cau- Experimental studies have shown that induced NO ses of heart failure. Diabetes related cardiomyopathy synthesis has a negative inotropic effect on cardiac cells has been defined as diabetic-mediated ventricular dy- [15] and that high levels of NO produced by inducible sfunction independently of any vascular disease and NOS (iNOS) are cytotoxic [16,17]. Recent studies have hypertension manifesting initially by diastolic dysfun- suggested that generation of nitric oxide (NO) in the en- ction, later by systolic dysfunction, and finally by heart docardium and myocardium regulates cardiac function failure [3]. In older studies, several mechanisms have in a paracrine and autocrine fashion [18,19]. In patients been discussed for onset and development of diabe- with cardiac dysfunction, can be attributed to excessive tic cardiomyopathy, it is thinked that oxidative stress NO production resulting from cytokine-induced expres- resulting from diabetes-mediated hyperglycemia, li- sion of iNOS in myocardial and vascular tissues [20,21]. Citation: Karadeniz T, Karadeniz M (2018) The Protective Effect of Resveratrol on Diabetic Cardiomy- opathy. Int J Diabetes Clin Res 5:089. doi.org/10.23937/2377-3634/1410089 Accepted: June 02, 2018: Published: June 04, 2018 Copyright: © 2018 Karadeniz T, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Karadeniz and Karadeniz. Int J Diabetes Clin Res 2018, 5:089 • Page 1 of 5 • DOI: 10.23937/2377-3634/1410089 ISSN: 2377-3634 Figure 1: Collagen turnover in the heart. Changed mechanical stress (σ) and oxidative stress may trigger TNF-α, TGF-β, and MMP. TNF-α stimulated the matrix metalloproteinases (MMP) and inhibit the tissue inhibitors of metalloproteinases (TIMP). In a result, MMP degrades collagens, but TIMP and myofibroblast inhibit collagen degradation and promote collagen synthesis, finally determine collagen ECM remodeling. The authors showed that expression of iNOS protein away from oxidative attack cardiovascular disorders. with a high prevalence of TNF-alpha protein expression Resveratrol (trans-3,5,4′-trihydroxystilbene), a polyphe- in cardiac myocytes related with cardiomyopathy. Some nolic compound and naturally occurring phytoalexin, researchers have previously shown that inducible NO has been designated the active agent [35] present in red synthase (iNOS) expression was significantly elevated in wine. In a previous study, resveratrol reduced the oxida- STZ diabetic rat hearts [22] and once induced, iNOS is tive stress and increased inducible nitric oxide synthase known to generate large amounts of NO until the enzy- (iNOS) mRNA expression which leading to reduction of me is degraded [23]. Some cytokines, as example IGF-I, cardiomyocyte apoptosis and infarct size. In another TGF-β1, connective tissue growth factor, platelet-deri- study researchers showed that induced effect of resve- ved growth factor, basic fibroblast growth factor, and ratrol via VEGF, iNOS and eNOS increased expression. epidermal growth factor, have been reported to both This situation provided significant cardioprotection as increase cellular proliferation (intestinal smooth muscle evidenced by the reduction of infarct area and increa- cells or myofibroblasts) and increase synthesis of ECM sed capillary density [36] in the rats myocardial tissue. or collagen [24,25]. The definite mechanism for the beneficial effects of- re sveratrol may be due to nitric oxide (NO) production in We know that the collagen content is increased in endothelial cells, and in the heart [37]. Giovannini, et al. myocardium of patients with cardiomyopathy, indica- [37] and Naderali, et al. [38] demonstrated that upre- ting changes in the collagenous framework of the he- gulation of NO is a principal factor for the anti-ischemic art [26,27]. Moreover, some authors found correlation function of resveratrol [39]. between the myocardial collagen and fasting plasma glucose, mRNA expressions of TGF beta [28]. Also, AGEs Hong and collageous showed that resveratrol sup- activate several critical molecular pathways, which trig- press the protein expression of TGF-B1, TGFR-I (TGF-B ger production of profibrogenic growth factors, con- type I receptor) and TGFR-II (TGF-B type II receptor) in nective tissue growth factor (CTGF), and TGFβ1 [29,30] renal epithelial cells [40]. In previosuly studies, resvera- as well as the inflammatory response. Transforming trol reduced the mRNA expression of the inflammatory growth factor (TGF)-β1 co-regulates MMP expression, mediators TNF-α and IL-1β, as well as the mRNA expres- it affects fibroblast proliferation and regulates ECM pro- sion of collagen type I and TGF-β in the dimethylnitrosa- mine model of liver fibrosis in rats [41,42]. Diabetic rats duction by promoting collagen synthesis and reducing supplemented with antioxidant showed decreased glu- collagen degradation (Figure 1) [31,32]. cose, HbA1c and increased the plasma insulin levels. As Aharinejad and collageous found that TGF-β1 expres- β-cells in particular, are highly susceptible to oxidative sion is increased in myocardium of DCM patients; and that stress, hyperglycemia and dyslipidemia [43-45] increase TGF-β1 stimulation in DCM cardiac tissue significantly in- in oxidative stress in STZ diabetic rat which may induce creased collagen type I but reduced MMP-1 [33]. Another apoptosis of β-cell. researchers were found that resveratrol can be significant In last a study has depicted that 8 weeks treatment upregulation of the protein expression profiles of vascular with resveratrol (2.5 mg/kg/day; ip.) improves diabetic endothelial growth factor (VEGF) [34]. heart function through reducing ventricular inflamma- For many years, new agents have been tried to get tion and remodeling [46]. Also in the other recent study, Karadeniz and Karadeniz. Int J Diabetes Clin Res 2018, 5:089 • Page 2 of 5 • DOI: 10.23937/2377-3634/1410089 ISSN: 2377-3634 it has been shown that resveratrol given at 2.5 mg/kg/ 2. Abbud ZA, Shindler DM, Wilson AC, Kostis JB (1995) Effect day orally for 4 weeks prevented from cardiac and va- of diabetes mellitus on short- and long-term mortality rates of patients with acute myocardial infarction: A statewide scular dysfunction in diabetic rats through its effect on study: Myocardial Infarction Data Acquisition System Study redox balance [47]. Group. Am Heart J 130: 51-58. Accumulating evidence suggests that hyperglycemia 3. Bauters C, Lamblin N, Mc Fadden EP, Van Belle E, Millaire induces ROS [46] and overproduction of ROS is associa- A, et al. (2003) Influence of diabetes mellitus on heart failu- ted with apoptosis in the diabetic
Load more

Recommended publications
  • Diabetes Reduces Left Ventricular Ejection Fraction-Irrespective Of
    European Journal of Endocrinology (2011) 165 945–951 ISSN 0804-4643 CLINICAL STUDY Diabetes reduces left ventricular ejection fraction-irrespective of presence and extent of coronary artery disease Niklas F Ehl1, Michael Ku¨hne1, Miriam Brinkert1, Jan Mu¨ller-Brand2 and Michael J Zellweger1 Departments of 1Cardiology and 2Nuclear Medicine, University Hospital, Petersgraben 4, CH - 4031 Basel, Switzerland (Correspondence should be addressed to M J Zellweger; Email: [email protected]) Abstract Background: It is not clear whether diabetes reduces systolic left ventricular function (left ventricular ejection fraction, LVEF) irrespective of coronary artery disease (CAD). The aim of this study was to compare the LVEF between diabetic and non-diabetic patients with respect to the extent of CAD. Methods and results: Consecutive patients undergoing stress myocardial perfusion SPECT (MPS) were evaluated. MPS was interpreted using a 20-segment model with a five-point scale to define summed stress score (SSS), summed rest score, and summed difference score. LVEF was measured by gated SPECT and then compared with respect to diabetic status and SSS categories. Of 2635 patients, data of 2400 was available. Of these, 24% were diabetic, mean age was 64G11y, and 31% were female. Diabetics had a significantly lower LVEF compared with non-diabetics regardless of the extent of CAD: 53G13 and 55G13% respectively (PZ0.001). Diabetics and non-diabetics did not differ significantly in the distribution of SSS categories. Diabetes was an independent predictor of decreased LVEF (odds ratio 1.6, 95% confidence interval 1.2–2.0; P!0.001). Conclusion: Diabetics had a lower LVEF than non-diabetics.
    [Show full text]
  • Treatment Options in Myocarditis and Inflammatory Cardiomyopathy
    Main topic Herz 2018 · 43:423–430 B. Maisch1 ·P.Alter2 https://doi.org/10.1007/s00059-018-4719-x 1 Fachbereich Medizin, Philipps-Universität Marburg und Herz- und Gefäßzentrum (HGZ) Marburg, Published online: 15 June 2018 Marburg, Germany © The Author(s) 2018 2 Klinik für Innere Medizin-Pneumologie und Intensivmedizin, UKGM und Philipps-Universität Marburg, Marburg, Germany Treatment options in myocarditis and inflammatory cardiomyopathy Focus on i. v. immunoglobulins In 2012 we reviewed the treatment op- proBNP) and high-sensitivity (hs) tro- curtain of diabetic cardiomyopathy, viral tions in (peri)myocarditis and inflamma- ponin T or I as cardiac biomarkers of heart disease with or without inflamma- tory cardiomyopathy in a special issue of heart failure and necrosis, respectively. tion can be hidden. But which of the this journal devoted to heart failure and Of note, cardiac MRI is an important factors is then the major etiological de- cardiomyopathies [1]. Now, 5 years later, method for clarifying the presence of terminant? itistimelyandappropriatetotakestock inflammation or fibrosis in addition to This issue also holds true for alcoholic of old and new data on this topic. function and pericardial effusion, but it cardiomyopathy [8]. In these patients, al- cannot substitute endomyocardial biopsy cohol consumption of more than 40 g/day Evolution of diagnoses for establishing an etiologically based di- in men and more than 20g/day in women agnosis [1–5]. For the diagnosis of viral formorethan5yearsisthesomewhat In 2013, experts of the European Soci- vs. autoreactive (nonviral) myocarditis arbitrary diagnostic determinant for the ety of Cardiology (ESC) working group and for the diagnosis of eosinophilic or label of alcoholic cardiomyopathy.
    [Show full text]
  • View Pdf Copy of Original Document
    Phenotype definition for the Vanderbilt Genome-Electronic Records project Identifying genetics determinants of normal QRS duration (QRSd) Patient population: • Patients with DNA whose first electrocardiogram (ECG) is designated as “normal” and lacking an exclusion criteria. • For this study, case and control are drawn from the same population and analyzed via continuous trait analysis. The only difference will be the QRSd. Hypothetical timeline for a single patient: Notes: • The study ECG is the first normal ECG. • The “Mildly abnormal” ECG cannot be abnormal by presence of heart disease. It can have abnormal rate, be recorded in the presence of Na-channel blocking meds, etc. For instance, a HR >100 is OK but not a bundle branch block. • Y duration = from first entry in the electronic medical record (EMR) until one month following normal ECG • Z duration = most recent clinic visit or problem list (if present) to one week following the normal ECG. Labs values, though, must be +/- 48h from the ECG time Criteria to be included in the analysis: Criteria Source/Method “Normal” ECG must be: • QRSd between 65-120ms ECG calculations • ECG designed as “NORMAL” ECG classification • Heart Rate between 50-100 ECG calculations • ECG Impression must not contain Natural Language Processing (NLP) on evidence of heart disease concepts (see ECG impression. Will exclude all but list below) negated terms (e.g., exclude those with possible, probable, or asserted bundle branch blocks). Should also exclude normalization negations like “LBBB no longer present.”
    [Show full text]
  • Diabetic Cardiomyopathy
    4 178 E Levelt and others Diabetic heart disease 178:4 R127–R139 Review MECHANISMS IN ENDOCRINOLOGY Diabetic cardiomyopathy: pathophysiology and potential metabolic interventions state of the art review Eylem Levelt1,†, Gaurav Gulsin1 , Stefan Neubauer2 and Gerry P McCann1 1British Heart Foundation Cardiovascular Research Centre, University of Leicester, Glenfield Hospital, Leicester, UK, 2University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Division of † Cardiovascular Medicine, Radcliffe Department of Medicine, Oxford, UK, (E Levelt is now at Multidisciplinary Correspondence Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and should be addressed Metabolic Medicine, University of Leeds, Leeds, UK) to E Levelt Email [email protected] Abstract Heart failure is a major cause of morbidity and mortality in type 2 diabetes. Type 2 diabetes contributes to the development of heart failure through a variety of mechanisms, including disease-specific myocardial structural, functional and metabolic changes. This review will focus on the contemporary contributions of state of the art non- invasive technologies to our understanding of diabetic cardiomyopathy, including data on cardiac disease phenotype, cardiac energy metabolism and energetic deficiency, ectopic and visceral adiposity, diabetic liver disease, metabolic modulation strategies and cardiovascular outcomes with new classes of glucose-lowering therapies. European Journal of Endocrinology European Journal European of Endocrinology (2018) 178, R127–R139 Introduction Diabetes has reached epidemic proportions and is now structural and haemodynamic changes are not directly among the top 10 causes of death worldwide (1). Type 2 attributable to other confounding factors such as coronary diabetes (T2D) is associated with an increased risk of both artery disease and hypertension, in patients with diabetes heart failure (HF) and cardiovascular mortality even in the (9).
    [Show full text]
  • Vascular Endothelial Dysfunction, a Major Mediator in Diabetic Cardiomyopathy
    www.nature.com/aps REVIEW ARTICLE Vascular endothelial dysfunction, a major mediator in diabetic cardiomyopathy Maura Knapp1, Xin Tu1 and Rongxue Wu1 Diabetes mellitus is currently a major public health problem. A common complication of diabetes is cardiac dysfunction, which is recognized as a microvascular disease that leads to morbidity and mortality in diabetic patients. While ischemic events are commonly observed in diabetic patients, the risk for developing heart failure is also increased, independent of the severity of coronary artery disease and hypertension. This diabetes-associated clinical entity is considered a distinct disease process referred to as “diabetic cardiomyopathy”. However, it is not clear how diabetes promotes cardiac dysfunction. Vascular endothelial dysfunction is thought to be one of the key risk factors. The impact of diabetes on the endothelium involves several alterations, including hyperglycemia, fatty acid oxidation, reduced nitric oxide (NO), oxidative stress, inflammatory activation, and altered barrier function. The current review provides an update on mechanisms that specifically target endothelial dysfunction, which may lead to diabetic cardiomyopathy. Keywords: cardiomyopathy; diabetes; diabetic cardiovascular complications; endothelium; vascular; heart failure; metabolism Acta Pharmacologica Sinica (2019) 40:1–8; https://doi.org/10.1038/s41401-018-0042-6 INTRODUCTION Clinical manifestations of diabetic cardiomyopathy Cardiovascular disease is a major cause of morbidity and mortality Diabetic cardiomyopathy affects both type 1 and type 2 diabetic in diabetic patients. It has long been established that diabetes patients and is characterized by a variety of functional and significantly increases the risk of cardiovascular disease, with structural changes in the heart. In early stages of the disease, left diabetic men being two times more likely to suffer from ventricular diastolic dysfunction (LVDD) is the most prevalent congestive heart failure (CHF) than non-diabetic individuals and cardiac complication [8, 9].
    [Show full text]
  • Diabetic Cardiomyopathy and Subclinical Cardiovascular Disease the Multi-Ethnic Study of Atherosclerosis (MESA)
    Pathophysiology/Complications ORIGINAL ARTICLE Diabetic Cardiomyopathy and Subclinical Cardiovascular Disease The Multi-Ethnic Study of Atherosclerosis (MESA) 1 4 ALAIN G. BERTONI, MD, MPH JOSEPH F. POLAK, MD, MPH eart failure has become a frequent 1 5 DAVID C. GOFF,JR., MD, PHD MOHAMMED F. SAAD, MD, MRCP manifestation of cardiovascular dis- 1 6 RALPH B. D’AGOSTINO,JR., PHD MOYSES SZKLO, MD, DRPH 2 ease (CVD) among individuals with IANG IU PHD 7 H K L , RUSSELL P. TRACY, PHD diabetes (1). As the prevalence of diabetes 1 8 W. GREGORY HUNDLEY, MD AVID ISCOVICK MD, MPH 3 D S. S , increases, it will probably emerge as one JOAO A. LIMA, MD of the principal causes of heart failure in the U.S. (2–4). There is significant evi- dence of the existence of “diabetic cardio- OBJECTIVE — Studies have demonstrated increased left ventricular mass (LVM) and dia- myopathy,” described classically as heart stolic dysfunction among diabetic patients without clinical cardiovascular disease (CVD), but failure in the absence of obstructive coro- few have assessed the potential contribution of subclinical CVD to ventricular abnormalities in nary disease but now more often defining diabetes. We examined whether diabetic cardiomyopathy is associated with subclinical athero- sclerosis and if abnormalities are found with impaired fasting glucose (IFG). ventricular abnormalities seen in individ- uals without coronary disease including RESEARCH DESIGN AND METHODS — LVM, end-diastolic volume (EDV), and increased left ventricular mass (LVM) and stroke volume were measured by magnetic resonance imaging (MRI), and atherosclerosis was impaired diastolic function (3,5–8). Pro- assessed by coronary artery calcium and carotid intima-media wall thickness in 4,991 partici- posed mechanisms include deleterious ef- pants in the Multi-Ethnic Study of Atherosclerosis, a cohort study of adults aged 45–84 without fects of hyperglycemia, hypertension, and prior CVD.
    [Show full text]
  • Diabetic Cardiomyopathy: Understanding the Independent Relationship Between Diabetes and Heart Failure
    HCA Healthcare Scholarly Commons Internal Medicine Research & Publications 2-7-2020 Diabetic Cardiomyopathy: Understanding the Independent Relationship Between Diabetes and Heart Failure W. Tyler Crawley Rage Geringer MD HCA Healthcare, [email protected] Jason Snarr DO HCA Healthcare, [email protected] Elizabeth Hicks MD HCA Healthcare Oliwier Dziadkowiec HCA Healthcare, [email protected] Follow this and additional works at: https://scholarlycommons.hcahealthcare.com/internal-medicine Part of the Cardiology Commons, Cardiovascular Diseases Commons, Endocrine System Diseases Commons, Endocrinology, Diabetes, and Metabolism Commons, and the Nutritional and Metabolic Diseases Commons Recommended Citation Crawley WT, Geringer R, Snarr J, Hicks ME, Dziadkowiec O. Diabetic cardiomyopathy: understanding the independent relationship between diabetes and heart failure. Poster presented at: ACP Colorado Chapter Meeting; February 6-8, 2020; Colorado Springs, CO. This Poster is brought to you for free and open access by the Research & Publications at Scholarly Commons. It has been accepted for inclusion in Internal Medicine by an authorized administrator of Scholarly Commons. Diabetic Cardiomyopathy: Understanding the Independent Relationship Between Diabetes and Heart Failure. W. Tyler Crawley, OMS-III; Rage Geringer, MD; Jason Snarr, DO; M. Elizabeth Hicks, MD, Oliwier Dziadkowiec, MD HCA Sky Ridge Medical Center, Hospital Corporation of America Graduate Medical Education, Rocky Vista University College of Osteopathic Medicine Introduction Figures Discussion Type 2 diabetes mellitus (DM) and heart failure (HF) are common chronic disorders that The development of DCM is related to the effects of DM systemically, on the myocardium, 1 affect 29 million and 6.5 million Americans respectively . While both often occur individually, and directly on cardiomyocytes3.
    [Show full text]
  • Case Report on Dilated Cardiomyopathy in Type 2 Diabetes Mellitus Patient with Hypothyroidism
    Case report on dilated cardiomyopathy in type 2 diabetes mellitus patient with hypothyroidism A. Bharath Kumar, M. S. Umashankar*, A. Porselvi Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, 603203, Kancheepuram district, Tamil nadu, India. Correspondence: M. S. Umashankar, Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, 603203, Kancheepuram district, Tamil nadu, India. E_mail: [email protected] ABSTRACT Dilated cardiomyopathy (DCM) is an idiopathic condition manifesting decreased contractility of heart, which is irreversible and slowly progressive. DCM, thyroid disorder and diabetes mellitus are the most interlinked symptomatology. Thyroid disease is a common endocrine disorder associated with diabetic cardiomyopathy. The complications which have been exhibited are contractile dysfunction, systolic dysfunction, ventricular dysfunction and diastolic dysfunction, ventricular diastolic and systolic dysfunction. A case study of a 75-year-old female patient visited the general medicine OPD with chief complaints of shortness of the breath, swelling of legs, chest discomfort, severe constipation, fatigue and palpitation. The patient was advised to have electrocardiogram which showed atrial fibrillation with ventricular tachycardia, and the chest X-ray which revealed cardiomegaly. The patient was also undergone echocardiogram which showed dilated cardiomyopathy with severely decreased left ventricular systolic function and a reduced left ventricular ejection fraction of 39%. Thyroid function test revealed a low hormone level. A regular treatment and continued patient’s follow up care were suggested to the patient, and she manifested a progressive development of her condition. The patient was prescribed with discharge medications, and advised for a follow-up care. Keywords: Dilated cardiomyopathy, thyroid diseases, diabetes mellitus, diastolic and systolic dysfunction.
    [Show full text]
  • Diabetic Cardiomyopathy: from Pathophysiology to Treatment
    Hellenic J Cardiol 2014; 55: 411-421 Review Article Diabetic Cardiomyopathy: From Pathophysiology to Treatment 1 1 2 2 KONSTANTINOS TRACHANAS , SKEVOS SIDERIS , CONSTANTINA AGGELI , EMMANOUIL POULIDAKIS , 2 2 1 KONSTANTINOS GATZOULIS , DIMITRIOS TOUSOULIS , IOANNIS KALLIKAZAROS 1Department of Cardiology, Hippokration General Hospital, 2First Department of Cardiology, National University of Athens, Hippokration General Hospital, Athens, Greece Key words: Diabetic he close relationship between di- As was demonstrated in the Framingham cardiomyopathy, abetes mellitus and heart failure Heart Study, diabetes is a strong and in- diastolic dysfunction, has been known for many years dependent risk factor for developing heart myocardial fibrosis, Tand includes many mechanisms. In 1881, failure, leading this group of patients to systolic dysfunction. Leyden first claimed that diabetic cardio- a worse prognosis. The risk of heart fail- myopathy is a common complication of ure was 2.4-fold and 5-fold higher in dia- diabetes and one worthy of attention. In betic men and women, respectively, than 1888, Mayer reported that diabetes is a in non-diabetic subjects. The incidence of disorder of metabolism that can lead to heart failure in diabetic patients is still in- heart disease. Finally, the term “diabet- creased even after adjustment for age, hy- ic cardiomyopathy” was introduced by pertension, obesity, coronary artery dis- Rubler in 1972, after post mortem stud- ease or dyslipidemia.5 The close correla- ies in diabetic patients with heart failure tion between diabetes and heart failure Manuscript received: in whom alcohol, hypertension, coronary has been demonstrated in many studies. November 21, 2012; disease and other structural heart disease In the United Kingdom Prospective Dia- Accepted: had been ruled out as possible causes.1 betes Study (UKPDS) an increased preva- June 1, 2014.
    [Show full text]
  • The Heart of Creatures Is the Foundation of Life, the Prince of All, the Sun of Their Microcosm, from Where All Vigor and Strength Does Flow
    The heart of creatures is the foundation of life, the Prince of all, the sun of their microcosm, from where all vigor and strength does flow. -William Harvey, De Motu Cordis, 1628 University of Alberta The Role of TIMPs in Heart Disease by Vijay Saradhi Kandalam A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy Department of Physiology ©Vijay Saradhi Kandalam Fall 2012 Edmonton, Alberta Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission. DEDICATION To family, friends, and colleagues who have supported my pursuit of realizing my potential. I would like to share this accomplishment with all of you, as without you I could not have achieved this. ABSTRACT Heart disease is a leading cause of morbidity and mortality in the world with a growing prevalence in a variety of manifestations. Many of the events that occur in the heart during the progression of disease have been explored to identify a causative mechanism to develop effective treatments and possibly a cure for heart disease.
    [Show full text]
  • The Mystery of Diabetic Cardiomyopathy: from Early Concepts and Underlying Mechanisms to Novel Therapeutic Possibilities
    International Journal of Molecular Sciences Review The Mystery of Diabetic Cardiomyopathy: From Early Concepts and Underlying Mechanisms to Novel Therapeutic Possibilities Petra Grubi´cRotkvi´c 1,* , Zrinka Planini´c 1 , Ana-Marija Liberati Pršo 1,2, Jozica Šiki´c 1,3, Edvard Gali´c 1,3 and Luka Rotkvi´c 4 1 Clinic of Internal Medicine, University Hospital “Sveti Duh”, Sveti Duh 64, 10000 Zagreb, Croatia; [email protected] (Z.P.); [email protected] (A.-M.L.P.); [email protected] (J.Š.); [email protected] (E.G.) 2 Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia 3 School of Medicine, University of Zagreb, Salata 2, 10000 Zagreb, Croatia 4 Magdalena Clinic for Cardiovascular Diseases, Ljudevita Gaja 2, 49217 Krapinske Toplice, Croatia; [email protected] * Correspondence: [email protected] Abstract: Diabetic patients are predisposed to diabetic cardiomyopathy, a specific form of cardiomy- opathy which is characterized by the development of myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis that develops independently of concomitant macrovascular and microvascular dia- betic complications. Its pathophysiology is multifactorial and poorly understood and no specific Citation: Grubi´cRotkvi´c,P.; therapeutic guideline has yet been established. Diabetic cardiomyopathy is a challenging diagnosis, Planini´c,Z.; Liberati Pršo, A.-M.; made after excluding other potential entities, treated with different pharmacotherapeutic agents Šiki´c,J.; Gali´c,E.; Rotkvi´c,L. targeting various pathophysiological pathways that need yet to be unraveled. It has great clinical The Mystery of Diabetic importance as diabetes is a disease with pandemic proportions. This review focuses on the potential Cardiomyopathy: From Early mechanisms contributing to this entity, diagnostic options, as well as on potential therapeutic inter- Concepts and Underlying ventions taking in consideration their clinical feasibility and limitations in everyday practice.
    [Show full text]
  • Contemporary Echocardiographic Techniques in Early Detection of Diabetic Cardiomyopathy
    Journal of Cardiology & Current Research Review article Open Access Contemporary echocardiographic techniques in early detection of diabetic cardiomyopathy Abstract Volume 1 Issue 5 - 2014 Diabetic cardiomyopathy is defined as heart failure independent of hypertension, Slavica Mitrovska, Biljana Lazeska coronary artery and valve disease. It has multifactorial etiology and the pathogenesis is Department of Internal Medicine, Military Hospital, Macedonia still incompletely understood. Structural changes lead to functional alterations of the left ventricle (LV) and diastolic dysfunction is the earliest sign. It has long asymptomatic Correspondence: Slavica Mitrovska, Department of Internal period, but with the time leads to reduced contractile function. Diagnosis of diabetic Medicine, Military Hospital, Macedonia ul. Sole Stojcev br. 1-2/8, cardiomyopathy is a challenge for cardiologists. As an entity, it exists for more than 4 1000 Skopje, Macedonia, Tel 38971385267, decades, but no single diagnostic method yet and no established standard diagnostic criteria. Email Current technology and methods are still subjects of modification and they are not routinely used in daily practice. Therefore, late diagnosis of cardiovascular complications of diabetes Received: September 08, 2014 | Published: October 13, 2014 is very often, even at the stage of overt heart failure. Echocardiography is a diagnostic method of choice, from practical and economic point of view, but conventional techniques-two-dimensional (2D), M-mode echocardiography and Pulsed-waved (PW) Doppler analysis have limitations and provide inconclusive results. Contemporary techniques-Tissue Doppler Imagine, Color M-mode, 2D Speckle Tracking, strain and strain-rate are more sensitive and relatively independent to the loading conditions methods that provides comprehensive assessment of myocardial tissue velocities.
    [Show full text]