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.

Diabetic Cardiomyopathy: Clinical and Metabolic Approach

2020 ◽  
Vol 19 ◽  
Author(s):  
Dragan B. Djordjevic ◽  
Goran Koracevic ◽  
Aleksandar D. Djordjevic ◽  
Dragan B. Lovic
Keyword(s):  
Heart Failure ◽  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Diabetic Cardiomyopathy ◽  
Treatment Options ◽  
Myocardial Strain ◽  
Clinical Manifestations ◽  
Left Ventricular ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors

Background:: Having in mind that diabetes mellitus (DM) and obesity are some of the greatest health challenges of the modern era, diabetic cardiomyopathy (DCM) is becoming more and more recognized in clinical practice. Main text:: Initially DM is asymptomatic, but it may progresses to diastolic, and then systolic left ventricular dysfunction, which results in congestive heart failure. A basic feature of this DM complication is the absence of haemodynamically sig-nificant stenosis of the coronary blood vessels. Clinical manifestations are the result of several metabolic disorders which are present during DM progression. The complexity of metabolic processes, along with numerous regulatory mechanisms, has been the subject of research which aims at discovering new diagnostic (e.g. myocardial strain with echocardiography and cardiac magnetic resonance) and treatment options. Adequate glycaemic control is not sufficient to prevent or reduce the progression of DCM. Contemporary hypoglycaemic medications, such as sodium-glucose transport protein 2 inhibitors significantly reduce the frequency of cardiovascular complications in patients with DM. Several studies have shown that, unlike the above stated medications, thiazolidinediones and dipeptidyl peptidase-4 inhibitors are associated with deteriora-tion of heart failure. Conclusion:: Imaging procedures, especially myocardial strain with echocardiography and cardiac magnetic resonance are useful to identify the early signs of DCM. Research and studies regarding new treatment options are still “in progress”.

scholarly journals A COMPREHENSIVE STUDY ON LITERATURE EVIDENCE, CLINICAL STUDIES AND PRACTICES OF HERBAL DRUGS FOR DIABETIC NEUROPATHY AND CARDIOMYOPATHY

2017 ◽  
Vol 10 (9) ◽  
pp. 30
Author(s):  
Arshiya Shamim ◽  
Hefazat Hussain Siddiqui ◽  
Tarique Mahmood ◽  
Paramdeep Bagga ◽  
Ranjan Kumar
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Diabetic Neuropathy ◽  
Diabetic Cardiomyopathy ◽  
Left Ventricular ◽  
Cardiac Autonomic Neuropathy ◽  
Diabetic Patients ◽  
Epidemic Disease ◽  
Complications Of Diabetes ◽  
Wide Range

  Diabetes mellitus is a worldwide epidemic disease that eventually advances to a chronic stage and affects different vital organs by intensifying the underlying pathological factors, and through the remodeling of the tissues by the generation of reactive oxygen species leading to the development of respective organ failure. Two such complications are painful neuropathy and cardiomyopathy; both of which are common and progressive complications of diabetes. The symptoms of peripheral neuropathy include tingling, burning, lancinating pain, hyperesthesia, and allodynia. The course of the disease progression may vary from intermittent, mild symptoms to severe chronic, and daily pain; which culminates into poor quality of life. Another complication of diabetes mellitus, diabetic cardiomyopathy, is defined as a ventricular dysfunction disorder that occurs in diabetic patients. The development of the disease is characterized by a hidden subclinical period, during which cellular, structural changes and abnormalities lead to diastolic dysfunction, followed by systolic dysfunction, and terminating into heart failure. Left ventricular hypertrophy, metabolic abnormalities, extracellular matrix changes, small vessel disease, cardiac autonomic neuropathy, insulin resistance, oxidative stress, and apoptosis are the most important pathological advancements that lead to diabetic cardiomyopathy. Various pharmaceutical agents from different pharmacological categories have been proposed for the symptomatic treatment of painful diabetic neuropathy; however, it is a herculean task to select a drug due to the wide range of choices and lack of consistent guidelines for treatment. Similarly, treatment of cardiomyopathy is based on the general therapeutic rules of management of heart failure and no specifications have yet been addressed for this condition. Therefore, more studies are required to improve our knowledge of these complex syndromes. From this perspective, this review is designed to delineate a general overview of neuropathy and cardiomyopathy, referring to the conventional therapies in use and possible unconventional, natural, herbal, and safe treatments for both the above-mentioned complications of diabetes.

Abstract 15: Glucose-Mediated Remodeling of Cardiac DNA Methylation

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Mark E Pepin ◽  
David K Crossman ◽  
Joseph P Barchue ◽  
Salpy V Pamboukian ◽  
Steven M Pogwizd ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Dna Methylation ◽  
Diabetic Cardiomyopathy ◽  
Left Ventricular ◽  
Epigenetic Mark ◽  
Gene Transcript ◽  
Transcript Levels ◽  
Glycemic Memory

To identify the role of glucose in the development of diabetic cardiomyopathy, we had directly assessed glucose delivery to the intact heart on alterations of DNA methylation and gene expression using both an inducible heart-specific transgene (glucose transporter 4; mG4H) and streptozotocin-induced diabetes (STZ) mouse models. We aimed to determine whether long-lasting diabetic complications arise from prior transient exposure to hyperglycemia via a process termed “glycemic memory.” We had identified DNA methylation changes associated with significant gene expression regulation. Comparing our results from STZ, mG4H, and the modifications which persist following transgene silencing, we now provide evidence for cardiac DNA methylation as a persistent epigenetic mark contributing to glycemic memory. To begin to determine which changes contribute to human heart failure, we measured both RNA transcript levels and whole-genome DNA methylation in heart failure biopsy samples (n = 12) from male patients collected at left ventricular assist device placement using RNA-sequencing and Methylation450 assay, respectively. We hypothesized that epigenetic changes such as DNA methylation distinguish between heart failure etiologies. Our findings demonstrated that type 2 diabetic heart failure patients (n = 6) had an overall signature of hypomethylation, whereas patients listed as ischemic (n = 5) had a distinct hypermethylation signature for regulated transcripts. The focus of this initial analysis was on promoter-associated CpG islands with inverse changes in gene transcript levels, from which diabetes (14 genes; e.g. IGFBP4) and ischemic (12 genes; e.g. PFKFB3) specific targets emerged with significant regulation of both measures. By combining our mouse and human molecular analyses, we provide evidence that diabetes mellitus governs direct regulation of cellular function by DNA methylation and the corresponding gene expression in diabetic mouse and human hearts. Importantly, many of the changes seen in either mouse type 1 diabetes or human type 2 diabetes were similar supporting a consistent mechanism of regulation. These studies are some of the first steps at defining mechanisms of epigenetic regulation in diabetic cardiomyopathy.

Abstract 16485: The Nitroxyl Donor 1-Nitrosocyclohexyl Acetate Limits Cardiac Superoxide Upregulation and Diastolic Dysfunction in a Mouse Model of Diabetic Cardiomyopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Rebecca H Ritchie ◽  
Nga Cao ◽  
Yung George Wong ◽  
Sarah Rosli ◽  
Helen Kiriazis ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mouse Model ◽  
Diastolic Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Ex Vivo ◽  
Systolic Function ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Lv Diastolic Dysfunction ◽  
The Impact

Nitroxyl (HNO), a redox congener of NO•, is a novel regulator of cardiovascular function combining vasodilator and positive inotropic properties. Our previous studies have demonstrated these properties occur concomitantly in the intact heart; HNO moreover also exhibits antihypertrophic and superoxide-suppressing actions. HNO donors may thus offer favorable actions in heart failure. The impact of chronic HNO donor administration has however yet to be reported in this context. We tested the hypothesis that the HNO donor 1-nitrosocyclohexyl acetate (1-NCA) limits cardiomyocyte hypertrophy and left ventricular (LV) diastolic dysfunction in a mouse model of diabetic cardiomyopathy in vivo. Male 6 week-old FVB/N mice received either streptozotocin (55 mg/kg/day i.p. for 5 days, n=17), to induce type 1 diabetes, or citrate vehicle (n=16). After 4 weeks of hyperglycemia, mice were allocated to 1-NCA therapy (83mg/kg/day i.p.) or vehicle, and followed for a further 4 weeks. As shown in the table, blood glucose was unaffected by 1-NCA. LV diastolic dysfunction was evident in diabetic mice, measured as echocardiography-derived A wave velocity, deceleration time and E:A ratio; LV systolic function was preserved. Diabetes-induced diastolic dysfunction was accompanied by increased LV cardiomyocyte size, hypertrophic and pro-fibrotic gene expression, and upregulation of LV superoxide. These characteristics of diabetic cardiomyopathy were largely prevented by 1-NCA treatment. Selectivity of 1-NCA as a donor of HNO versus NO• was demonstrated by the sensitivity of the coronary vasodilation response of 1-NCA to the HNO scavenger L-cysteine (4mM), but not to the NO• scavenger hydroxocobalamin (50μM), in the normal rat heart ex vivo (n=3-7). Collectively, our studies provide the first evidence that HNO donors may represent a promising new strategy for the treatment of diabetic cardiomyopathy, and implies their therapeutic efficacy in settings of chronic heart failure.

scholarly journals Development and Pilot-Testing of a Patient Decision Aid for Left Ventricular Assist Device Placement

2016 ◽  
Author(s):  
Kristin Kostick ◽  
Estevan D. Delgado ◽  
Lidija A. Wilhelms ◽  
Courtenay R. Bruce ◽  
Jerry D. Estep ◽  
...  
Keyword(s):  
Heart Failure ◽  
Decision Aid ◽  
Treatment Options ◽  
Left Ventricular ◽  
Assist Device ◽  
Heart Failure Treatment ◽  
Ventricular Assist ◽  
Risks And Benefits ◽  
Patient Decision ◽  
Left Ventricular Assist

Background Studies indicate suboptimal patient understanding of the capabilities, lifestyle implications, and risks of LVAD therapy. This paper describes the development methodology and pilot-testing of a decision aid for Left Ventricular Assist Device (LVAD) placement, combining traditional needs-assessment with a novel user- centered approach. Methods and Results We developed the decision aid in line with the Ottawa Decision Support Framework (ODSF) and the International Patient Decision Aids Standards (IPDAS) for ensuring quality, patient-centered content. Structured interviews were conducted with patients, caregivers, candidates for LVAD treatment, and expert clinicians (n=71) to generate content based on patient values and decisional needs, and providers’ perspectives on knowledge needs for informed consent. The aid was alpha tested through cognitive interviews (n=5) and acceptability tested with LVAD patients (n=10), candidates (n=10), and clinicians (n=13). Patients, caregivers and clinicians reported they would recommend the aid to patients considering treatment options for heart failure. Patients and caregivers agreed that the decision aid is a balanced tool presenting risks and benefits of LVAD treatment and generating discussion about aspects of heart failure treatment that matter most to patients. Conclusion We identified gaps in knowledge about heart failure treatment options, including diagnosis, decision-making, surgery, post-operative maintenance and lifestyle changes. Challenges included presenting risks and benefits for informed decision making without frightening patients and circumventing reflection, and balancing an emphasis on LVAD with other alternative treatment options like comfort- directed palliative and supportive care.

scholarly journals Effect of Acute Hyperglycemia on Left Ventricular Contractile Function in Diabetic Patients with and without Heart Failure: Two Randomized Cross-Over Studies

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e53247 ◽  
Author(s):  
Roni Nielsen ◽  
Helene Nørrelund ◽  
Ulla Kampmann ◽  
Hans Erik Bøtker ◽  
Niels Møller ◽  
...  
Keyword(s):  
Heart Failure ◽  
Contractile Function ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Acute Hyperglycemia

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.

Nocturnal Hypertension and Heart Failure: Mechanisms, Evidence, and New Treatments

Hypertension ◽  
2021 ◽  
Author(s):  
Kazuomi Kario ◽  
Bryan Williams
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiovascular Events ◽  
Treatment Options ◽  
Left Ventricular ◽  
Nocturnal Hypertension ◽  
Reduced Ejection Fraction ◽  
Nighttime Blood Pressure ◽  
Evidence Based Treatments ◽  
New Treatments

Heart failure (HF) is a common condition with an increasing prevalence. Despite a variety of evidence-based treatments for patients with HF with reduced ejection fraction, morbidity and mortality rates remain high. Furthermore, there are currently no treatments that have yet been shown to reduce complication and death rates in patients who have HF with preserved ejection fraction. Hypertension is a common comorbidity in patients with HF, contributing to disease development and prognosis. For example, hypertension is closely associated with the development of left ventricular hypertrophy, which an important precursor of HF. In particular, nighttime blood pressure (BP) appears to be an important, modifiable risk factor. Both nighttime BP and an abnormal circadian pattern of nighttime BP dipping have been shown to predict development of HF and the occurrence of cardiovascular events, independent of office BP. Key mechanisms for this association include sodium handling/salt sensitivity and increased sympathetic activation. These pathogenic mechanisms are targeted by several new treatment options, including sodium-glucose cotransporter 2 inhibitors, angiotensin receptor neprilysin inhibitors, mineralocorticoid receptor antagonists, and renal denervation. All of these could form part of antihypertensive strategies designed to control nighttime BP and contribute to the goal of achieving perfect 24-hour BP management. Nevertheless, additional research is needed to determine the effects of reducing nighttime BP and improving the circadian BP profile on the rate of HF, other cardiovascular events, and mortality.

Surgical Alternatives for Patients with Heart Failure

1993 ◽  
Vol 4 (2) ◽  
pp. 244-259
Author(s):  
Rita Vargo ◽  
Josephine M. Dimengo
Keyword(s):  
Heart Failure ◽  
Coronary Artery ◽  
Ventricular Remodeling ◽  
Artery Bypass ◽  
Treatment Options ◽  
Myocardial Revascularization ◽  
Left Ventricular ◽  
Surgical Interventions ◽  
Cardioverter Defibrillator ◽  
Artery Disease

Chronic heart failure is a progressive syndrome characterized by diffuse coronary artery disease (CAD) or left ventricular failure not amenable to acute interventions of myocardial revascularization. A spectrum of treatment options is available to such patients. Medical therapies consist largely of pharmacologic alternatives and are used in the early stages of heart failure to slow the processes of ventricular remodeling. Surgical interventions are used as adjunctive therapies in the later stages of heart failure. These procedures include coronary endarterectomy, high-risk surgical revascularization, automatic internal cardioverter-defibrillator insertion (Coronary Artery Bypass Grafting in Conjunction with Implantable Cardioverter Defibrillator Trial), cardiac transplantation, and dynamic cardiomyoplasty. This article provides an overview of each of these surgical therapies. Indications for each procedure and patient selection criteria are outlined. A description of each surgical procedure is included. Guidelines for postoperative nursing care are provided, and postoperative complications are discussed

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