Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 71
Filter
1.
ABCS health sci ; 46: e021307, 09 fev. 2021. ilus, tab
Article in English | LILACS | ID: biblio-1349413

ABSTRACT

Diabetes mellitus (DM) is considered a 21st century pandemic and is often associated with cardiovascular disease (CVD). The aim of this integrative review was to analyze the cardioprotective effects of phosdodiesterase-5 (PDE5i) inhibitors in experimental diabetes models. The articles were selected from the PubMed, SciELO and LILACS databases from 2014 to 2019. The following descriptors were used in combination with the Boolean operators: Diabetes mellitus experimental AND Phosphodiesterase 5 inhibitors; Diabetic cardiomyopathies AND Phosphodiesterase 5 inhibitors. An initial sample of 155 articles was obtained, of which six met the criteria for the synthesis of the review. The studies analyzed showed that treatment with PDE5i in experimental models, resulted in positive effects on cardiac function and metabolic parameters. Similar results have also been seen in humans. The reduction in cardiac hypertrophy, apoptosis of cardiomyocytes, pro-inflammatory factors and oxidative stress and the modulation of transcription factors involved in diabetes homeostasis, were prevalent among studies. The mechanisms of action involved in cardioprotection have not yet been fully elucidated, however the restoration of the activated cyclic guanosine monofate (cGMP) pathway by soluble guanylate cyclase (sGC) via nitric oxide (NO) was a common mechanism among the studies.


O Diabetes mellitus (DM) é considerado uma pandemia do século XXI e está frequentemente associado às doenças cardiovasculares (DCVs). O objetivo desta revisão integrativa foi analisar os efeitos cardioprotetores de inibidores da fosdodiesterase 5 (PDE5i) em modelos de diabetes experimental. Os artigos foram selecionados nas bases de dados PubMed, SciElo e LILACS no período de 2014 a 2019. Foram utilizados os seguintes descritores combinados com os operadores booleanos: Diabetes mellitus experimental AND Phosphodiesterase 5 inhibitors; Diabetic cardiomyopathies AND Phosphodiesterase 5 inhibitors. Foi obtida uma amostra inicial de 155 artigos, dos quais seis se enquadraram nos critérios para a síntese da revisão. Os estudos analisados evidenciaram que o tratamento com os PDEi5 em modelos experimentais, resultou em efeitos positivos sobre a função cardíaca e parâmetros metabólicos. Resultados semelhantes também foram observados em humanos. A redução da hipertrofia cardíaca, apoptose de cardiomiócitos, fatores pró-inflamatórios e estresse oxidativo e a modulação de fatores de transcrição envolvidos na homeostasia do diabetes, foram achados prevalentes entre os estudos. Os mecanismos de ação envolvidos na cardioproteção ainda não foram totalmente elucidados, contudo a restauração da via da guanosina monofato cíclica ativada (GMPc) pela Guanilato ciclase solúvel (GCs) via Óxido Nítrico (NO) foi um mecanismo comum entre os estudos.


Subject(s)
Humans , Diabetes Mellitus, Experimental , Diabetic Cardiomyopathies , Phosphodiesterase 5 Inhibitors , Noncommunicable Diseases
2.
Clinics ; 76: e2669, 2021. graf
Article in English | LILACS | ID: biblio-1278915

ABSTRACT

OBJECTIVES: This study aimed to explore the efficacy of combination treatment with dendrobium mixture and metformin (Met) in diabetic cardiomyopathy (DCM) and its effects on NEAT1 and the Nrf2 signaling pathway. METHODS: H9c2 cells were maintained in medium supplemented with either low (5.5 mmol/L) or high (50 mmol/L) glucose. Male Sprague-Dawley rats were fed a high-glucose diet and administered a single, low dose of streptozotocin (35 mg/kg) via intraperitoneal injection to induce the development of DM. After induction of DM, the rats were treated with dendrobium mixture (10 g/kg) and Met (0.18 g/kg) daily for 4 weeks. Next, quantitative reverse transcription (qRT)-PCR and western blotting were performed to evaluate the expression levels of target genes and proteins. Flow cytometry was performed to assess apoptosis, and hematoxylin and eosin staining was performed to evaluate the morphological changes in rat cardiac tissue. RESULTS: In patients with diabetes mellitus (DM) and myocardial cells and heart tissues from rats with high glucose-induced DM, NEAT1 was downregulated, and the expression levels of Nrf2 were decreased (p<0.01, p<0.001). The combination of dendrobium mixture and Met upregulated the expression of NEAT1 which upregulated Nrf2 by targeting miR-23a-3p, resulting in reduced apoptosis and improved cardiac tissue morphology (p<0.01, p<0.001). CONCLUSION: Dendrobium mixture and Met upregulated the expression of NEAT1 in DCM, thereby inhibiting apoptosis of myocardial cells.


Subject(s)
Humans , Animals , Male , Rats , Dendrobium , MicroRNAs , Diabetes Mellitus , Diabetic Cardiomyopathies/genetics , Diabetic Cardiomyopathies/drug therapy , Metformin , Apoptosis , RNA, Long Noncoding/genetics
3.
Article in Chinese | WPRIM | ID: wpr-879143

ABSTRACT

Pharmacology network was used to investigate the common key target and signaling pathway of Notoginseng Radix et Rhizoma in the protection against diabetic nephropathy(DN), diabetic encephalopathy(DE) and diabetic cardiomyopathy(DCM). The chemical components of Notoginseng Radix et Rhizoma were obtained through TCMSP database and literature mining, and SwissTargetPrediction database was used to predict potential targets of Notoginseng Radix et Rhizoma. The disease targets of DN, DE and DCM were obtained through OMIM and GeneCards databases. The overlapped targets of component targets and disease targets of DN, DE and DCM were obtained, and the network of "chemical component-target-disease" was established. The enriched GO and KEGG of the overlapped genes were investigated by using ClueGo plug-in with Cytoscape. At the same time, the PPI network was constructed through STRING database, and the common key targets for the treatment of three diseases by Notoginseng Radix et Rhizoma were obtained through topological parametric mathematical analysis by Cytoscape. A total of 166 chemical components and 835 component targets were screened out from Notoginseng Radix et Rhizoma. Briefly, 216, 194 and 230 disease targets of DN, DE and DCM were collected, respectively. And 54, 45 and 57 overlapped targets were identified when overlapping these disease targets with component targets of Notoginseng Radix et Rhizoma, respectively. Enrichment analysis indicated that the AGE-RAGE signaling pathway and FoxO signaling pathway were the common pathways in the protection of Notoginseng Radix et Rhizoma against DN, DE and DCM. Network analysis of the overlapped targets showed that TNF, STAT3, IL6, VEGFA, MAPK8, CASP3 and SIRT1 were identified as key targets of Notoginseng Radix et Rhizoma against DN, DE and DCM, the selected key targets were verified by literature review, and it was found that TNF, IL6, VEGFA, CASP3 and SIRT1 had been reported in the literature. In addition, there were the most compounds corresponding to the commom core target STAT3, indicating that more compounds in Notoginseng Radix et Rhizoma could regulate STAT3. This study indicated that Notoginseng Radix et Rhizoma potentially protected against DN, DE and DCM through regulating AGE-RAGE signaling pathway and FoxO signaling pathway and 7 common targets including TNF, STAT3, IL6, VEGFA, MAPK8, CASP3 and SIRT1. This study provided a reference for the research of "different diseases with same treatment" and also elucidated the potential mechanism of Notoginseng Radix et Rhizoma against DN, DE and DCM.


Subject(s)
Brain Diseases , Diabetes Mellitus , Diabetic Cardiomyopathies/genetics , Diabetic Nephropathies/genetics , Humans , Research Design , Signal Transduction
4.
Rev. Soc. Argent. Diabetes ; 54(supl. 2): 91-106, mayo - ago. 2020. tab
Article in Spanish | LILACS, BINACIS | ID: biblio-1122959

ABSTRACT

Desde que el estudio Framingham en 1974 reportó un aumento de dos a cinco veces en el riesgo de desarrollar insuficiencia cardíaca (IC) en pacientes con diabetes mellitus (DM), otros estudios observacionales confirmaron esta asociación que ha tomado gran visibilidad en los últimos años a partir de los resultados de los estudios de seguridad cardiovascular de las drogas antidiabéticas. La IC se define como un síndrome clínico que resulta del deterioro funcional o estructural del llenado ventricular o la eyección de sangre. Puede clasificarse según la fracción de eyección, la presencia de síntomas y la limitación de la actividad física. Existen distintos factores asociados a la IC en personas con DM como la edad, la antigüedad de la enfermedad, la utilización de insulina, la enfermedad coronaria, la hipertensión arterial, la enfermedad arterial periférica, el aumento de creatinina, el escaso control glucémico, la albuminuria y la obesidad. A su vez la IC se asocia a insulinorresistencia y a estados disglucémicos que se consideran de riesgo para el desarrollo de DM. En la fisiopatología están implicados el sistema nervioso simpático, el sistema renina angiotensina aldosterona, los péptidos natriuréticos, alteraciones renales, remodelación del ventrículo izquierdo, miocardiopatía diabética, neuropatía autonómica cardíaca y la inflamación. El diagnóstico de IC es clínico; los estudios complementarios orientan en el diagnóstico etiológico y son útiles en el seguimiento. El buen control glucémico es importante pero no suficiente para reducir el desarrollo de IC. Se ha descripto que algunos antidiabéticos podrían incrementar el riesgo de falla cardíaca y, por el contrario, otros tendrían un efecto beneficioso. El tratamiento de la IC no difiere de una persona sin DM. Dado que el pronóstico de la IC en los pacientes con DM es más severo, los esfuerzos deben centrarse en prevenir, diagnosticar y tratar los factores de riesgo cardiovascular para reducir el desarrollo de IC.


Since the Framingham study in 1974 reported a 2 to 5 fold increase in the risk of developing heart failure (HF) in patients with diabetes mellitus (DM), other observational studies confirmed this association that has gained great visibility in recent years from of the results of cardiovascular safety studies of antidiabetic drugs. HF is defined as a clinical syndrome that results from functional or structural deterioration of ventricular filling or blood ejection. It can be classified according to the ejection fraction, the presence of symptoms and the limitation to physical activity. There are different factors associated with HF in people with DM such as age, duration of the disease, insulin use, coronary heart disease, high blood pressure, peripheral arterial disease, increased creatinine, poor glycemic control, albuminuria and obesity. In turn, HF is associated with insulin resistance and dysglycemic states that are considered of risk for the development of DM. Pathophysiology involves the sympathetic nervous system, the renin angiotensin aldosterone system, natriuretic peptides, kidney abnormalities, left ventricular remodeling, diabetic cardiomyopathy, autonomic cardiac neuropathy, and inflammation. The diagnosis of HF is clinical, complementary studies guide the etiological diagnosis and are useful for follow-up. Good glycemic control is important but not sufficient to reduce the development of HF. It has been described that some antidiabetics could increase the risk of heart failure, while others would have a beneficial effect. The treatment of HF does not differ from a person without DM. Since the prognosis of HF in patients with DM is more severe, efforts should be focused on preventing, diagnosing and treating cardiovascular risk factors, to reduce the development of HF


Subject(s)
Humans , Diabetes Mellitus, Type 2 , Therapeutics , Coronary Disease , Diabetic Cardiomyopathies , Heart Failure
5.
Article in English | WPRIM | ID: wpr-811150

ABSTRACT

Mitochondrial medicine is increasingly discussed as a promising therapeutic approach, given that mitochondrial defects are thought to contribute to many prevalent diseases and their complications. In individuals with diabetes mellitus (DM), defects in mitochondrial structure and function occur in many organs throughout the body, contributing both to the pathogenesis of DM and complications of DM. Diabetic cardiomyopathy (DbCM) is increasingly recognized as an underlying cause of increased heart failure in DM, and several mitochondrial mechanisms have been proposed to contribute to the development of DbCM. Well established mechanisms include myocardial energy depletion due to impaired adenosine triphosphate (ATP) synthesis and mitochondrial uncoupling, and increased mitochondrial oxidative stress. A variety of upstream mechanisms of impaired ATP regeneration and increased mitochondrial reactive oxygen species have been proposed, and recent studies now also suggest alterations in mitochondrial dynamics and autophagy, impaired mitochondrial Ca²⁺ uptake, decreased cardiac adiponectin action, increased O-GlcNAcylation, and impaired activity of sirtuins to contribute to mitochondrial defects in DbCM, among others. In the current review, we present and discuss the evidence that underlies both established and recently proposed mechanisms that are thought to contribute to mitochondrial dysfunction in DbCM.


Subject(s)
Adenosine Triphosphate , Adiponectin , Autophagy , Diabetes Mellitus , Diabetic Cardiomyopathies , Heart Failure , Mitochondria , Mitochondrial Dynamics , Oxidative Stress , Reactive Oxygen Species , Regeneration , Sirtuins
6.
Article in English | WPRIM | ID: wpr-811149

ABSTRACT

No abstract available.


Subject(s)
Diabetic Cardiomyopathies , MicroRNAs
7.
Article in English | WPRIM | ID: wpr-811138

ABSTRACT

BACKGROUND: Recent studies have shown that microRNAs (miRNAs) are involved in the process of cardiomyocyte apoptosis. We have previously reported that granulocyte-colony stimulating factor (G-CSF) ameliorated diastolic dysfunction and attenuated cardiomyocyte apoptosis in a rat model of diabetic cardiomyopathy. In this study, we hypothesized a regulatory role of cardiac miRNAs in the mechanism of the anti-apoptotic effect of G-CSF in a diabetic cardiomyopathy rat model.METHODS: Rats were given a high-fat diet and low-dose streptozotocin injection and then randomly allocated to receive treatment with either G-CSF or saline. H9c2 rat cardiomyocytes were cultured under a high glucose (HG) condition to induce diabetic cardiomyopathy in vitro. We examined the extent of apoptosis, miRNA expression, and miRNA target genes in the myocardium and H9c2 cells.RESULTS: G-CSF treatment significantly decreased apoptosis and reduced miR-34a expression in diabetic myocardium and H9c2 cells under the HG condition. G-CSF treatment also significantly increased B-cell lymphoma 2 (Bcl-2) protein expression as a target for miR-34a. In addition, transfection with an miR-34a mimic significantly increased apoptosis and decreased Bcl-2 luciferase activity in H9c2 cells.CONCLUSION: Our results indicate that G-CSF might have an anti-apoptotic effect through down-regulation of miR-34a in a diabetic cardiomyopathy rat model.


Subject(s)
Animals , Apoptosis , Diabetic Cardiomyopathies , Diet, High-Fat , Down-Regulation , Glucose , Granulocyte Colony-Stimulating Factor , In Vitro Techniques , Luciferases , Lymphoma, B-Cell , MicroRNAs , Models, Animal , Myocardium , Myocytes, Cardiac , Rats , Streptozocin , Transfection
8.
Article in English | WPRIM | ID: wpr-786081

ABSTRACT

The heart faces the challenge of adjusting the rate of fatty acid uptake to match myocardial demand for energy provision at any given moment, avoiding both too low uptake rates, which could elicit an energy deficit, and too high uptake rates, which pose the risk of excess lipid accumulation and lipotoxicity. The transmembrane glycoprotein cluster of differentiation 36 (CD36), a scavenger receptor (B2), serves many functions in lipid metabolism and signaling. In the heart, CD36 is the main sarcolemmal lipid transporter involved in the rate-limiting kinetic step in cardiac lipid utilization. The cellular fatty acid uptake rate is determined by the presence of CD36 at the cell surface, which is regulated by subcellular vesicular recycling from endosomes to the sarcolemma. CD36 has been implicated in dysregulated fatty acid and lipid metabolism in pathophysiological conditions, particularly high-fat diet-induced insulin resistance and diabetic cardiomyopathy. Thus, in conditions of chronic lipid overload, high levels of CD36 are moved to the sarcolemma, setting the heart on a route towards increased lipid uptake, excessive lipid accumulation, insulin resistance, and eventually contractile dysfunction. Insight into the subcellular trafficking machinery of CD36 will provide novel targets to treat the lipid-overloaded heart. A screen for CD36-dedicated trafficking proteins found that vacuolar-type H⁺-ATPase and specific vesicle-associated membrane proteins, among others, were uniquely involved in CD36 recycling. Preliminary data suggest that these proteins may offer clues on how to manipulate myocardial lipid uptake, and thus could be promising targets for metabolic intervention therapy to treat the failing heart.


Subject(s)
Cardiomyopathies , Diabetic Cardiomyopathies , Endosomes , Glycoproteins , Heart , Insulin Resistance , Lipid Metabolism , R-SNARE Proteins , Receptors, Scavenger , Recycling , Sarcolemma
9.
Rev. Assoc. Med. Bras. (1992) ; 65(1): 61-69, Jan. 2019. tab, graf
Article in English | LILACS | ID: biblio-985004

ABSTRACT

SUMMARY Although long ago described, there is no established consensus regarding the real existence of Diabetic Cardiomyopathy (CMPDM). Due to its complex pathophysiology, it has been difficult for clinical and experimental research to establish clear connections between diabetes mellitus (DM) and heart failure (HF), as well as to solve the mechanisms of the underlying myocardial disease. However, the epidemiological evidence of the relationship of these conditions is undisputed. The interest in understanding this disease has intensified due to the recent results of clinical trials evaluating new glucose-lowering drugs, such as sodium-glucose transporter inhibitors 2, which demonstrated favorable responses considering the prevention and treatment of HF in patients with DM. In this review we cover aspects of the epidemiology of CMPDM and its possible pathogenic mechanisms, as well as, present the main cardiac phenotypes of CMPDM (HF with preserved and reduced ejection fraction) and implications of the therapeutic management of this disease.


RESUMO Apesar de há muito tempo descrita, não existe consenso estabelecido quanto à real existência da cardiomiopatia diabética (CMPDM). Devido à sua complexa fisiopatologia, tem sido árduo à pesquisa clínica e experimental estabelecer conexões claras entre diabetes mellitus (DM) e insuficiência cardíaca (IC), assim como solucionar os mecanismos da doença subjacente do miocárdio. No entanto, as evidências epidemiológicas da relação dessas condições são incontestáveis. O interesse em compreender melhor essa doença tem recrudescido devido aos recentes resultados de ensaios clínicos avaliando novos fármacos hipoglicemiantes, como os inibidores do transportador de sódio-glicose 2, que demonstraram respostas favoráveis, considerando-se a prevenção e tratamento da IC em pacientes portadores de DM. Nesta revisão, percorremos aspectos da epidemiologia da CMPDM e de seus possíveis mecanismos patogênicos, além de apresentarmos os principais fenótipos cardíacos da CMPDM (IC com fração de ejeção preservada e reduzida) e implicações do manejo terapêutico desta doença.


Subject(s)
Humans , Diabetic Cardiomyopathies/diagnostic imaging , Phenotype , Echocardiography , Risk Factors , Evidence-Based Medicine , Diabetic Cardiomyopathies/therapy , Diabetic Cardiomyopathies/epidemiology
10.
Article in English | WPRIM | ID: wpr-765654

ABSTRACT

Diabetes mellitus increases the risk for the development of heart failure even in the absence of coronary artery disease and hypertension, a cardiac entity termed diabetic cardiomyopathy (DC). Clinically, DC is increasingly recognized and typically characterized by concentric cardiac hypertrophy and diastolic dysfunction, ultimately resulting in heart failure with preserved ejection fraction (HFpEF) and potentially even heart failure with reduced ejection fraction (HFrEF). Numerous molecular mechanisms have been proposed to underlie the alterations in myocardial structure and function in DC, many of which show similar alterations in the failing heart. Well investigated and established mechanisms of DC include increased myocardial fibrosis, enhanced apoptosis, oxidative stress, impaired intracellular calcium handling, substrate metabolic alterations, and inflammation, among others. In addition, a number of novel mechanisms that receive increasing attention have been identified in recent years, including autophagy, dysregulation of microRNAs, epigenetic mechanisms, and alterations in mitochondrial protein acetylation, dynamics and quality control. This review aims to provide an overview and update of established underlying mechanisms of DC, as well as a discussion of recently identified and emerging mechanisms that may also contribute to the structural and functional alterations in DC.


Subject(s)
Acetylation , Apoptosis , Autophagy , Calcium , Cardiomegaly , Coronary Artery Disease , Diabetes Mellitus , Diabetic Cardiomyopathies , Epigenomics , Fibrosis , Heart , Heart Failure , Hypertension , Inflammation , MicroRNAs , Mitochondrial Proteins , Oxidative Stress , Quality Control
11.
Article in Korean | WPRIM | ID: wpr-761473

ABSTRACT

There is a close relationship between diabetes mellitus and heart failure, both of which are known to increase morbidity and mortality. Diabetes can cause or aggravate heart failure, and heart failure can precipitate diabetes. Diabetes mellitus causes structural and functional changes in the heart, such as fibrosis of the myocardium and left ventricular dysfunction. The mechanisms of diabetic cardiomyopathy are metabolic disturbance, myocardial fibrosis, microvascular disease, and autonomic dysfunction. Improper blood glucose control leads to deterioration of heart failure, but the role of strict glycemic control in reducing heart failure is unclear. The role of SGLT2 inhibitors in reducing the incidence of heart failure is of great importance in the treatment of diabetic patients. However, further long-term follow-up and safety studies are needed.


Subject(s)
Blood Glucose , Diabetes Complications , Diabetes Mellitus , Diabetic Cardiomyopathies , Fibrosis , Follow-Up Studies , Heart Failure , Heart , Humans , Incidence , Mortality , Myocardium , Ventricular Dysfunction, Left
12.
Rev. colomb. cardiol ; 25(1): 51-54, ene.-feb. 2018. tab
Article in Spanish | LILACS, COLNAL | ID: biblio-959945

ABSTRACT

Resumen Objetivo: Estimar la prevalencia de pacientes con probable miocardiopatía diabética (sin exigir biopsia endomiocárdica), analizando sus características y comparándolas con pacientes no diabéticos con insuficiencia cardiaca idiopática. Métodos: Estudio retrospectivo sobre una cohorte de 270 pacientes que ingresaron de manera consecutiva por insuficiencia cardiaca. De estos se excluyeron del estudio todos aquellos que tuvieran una causa conocida de insuficiencia cardiaca (cardiopatía isquémica, hipertensiva, hipertrófica, valvular u otras). En total 58 pacientes, 18 de los cuales eran diabéticos (la causa de la insuficiencia cardiaca pudo ser la miocardiopatía diabética) y 40 sin diabetes (insuficiencia cardiaca idiopática). Se procedió a comparar las características entre ambos grupos. El análisis estadístico y la comparación de las distintas variables se realizó mediante el programa SPSS versión 20.0. Resultados: De 270 pacientes estudiados, 18 podrían haber sido diagnosticados con miocardiopatía diabética, lo que supone hasta un 6% de la insuficiencia cardiaca en esta serie. Conclusiones: Se considera que este estudio puede hacer reflexionar sobre la prevalencia global de la miocardiopatía diabética, sus características y sus dificultades diagnósticas.


Abstract Objective: To determine the prevalence of patients with probable diabetic cardiomyopathy (without requesting an endomyocardial biopsy), as well as to analyse its characteristics and comparing them with non-diabetic patients with idiopathic heart failure. Methods: A retrospective study was conducted on a cohort of 270 patients consecutively admitted to hospital due to heart failure. Excluded from the study were those who had a known cause of heart failure (ischaemic, hypertensive, hypertrophic, valvular, or other causes of heart disease). This left a total of 58 patients, 18 of whom were diabetics (the cause of heart failure could be due to diabetic cardiomyopathy) and 40 non-diabetics (idiopathic heart failure). A comparison was made between the characteristics of both groups. The statistical analysis and the comparison of the different variables were performed using Version 20.0 of the SPSS program. Results: Of the 270 patients studied, 18 could have been diagnosed with diabetic cardiomyopathy, which would be 6% of the cardiac failures in this series. Conclusions: It is believed that this study can lead to reflecting on the overall prevalence of diabetic cardiomyopathy, its characteristics, and the difficulties in its diagnosis.


Subject(s)
Humans , Male , Female , Diabetes Mellitus , Heart Failure , Myocardial Ischemia , Diabetic Cardiomyopathies , Cardiomyopathies
13.
Article in English | WPRIM | ID: wpr-772782

ABSTRACT

OBJECTIVE@#To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyopathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy.@*METHODS@#Sixty Sprague-Dawley (SD) rats were randomly divided into six groups: a normal control group (NC), an obesity group (OB), a diabetic cardiomyopathy group (DCM), a tea polyphenol group (TP), an obesity tea polyphenol treatment group (OB-TP), and a diabetic cardiomyopathy tea polyphenol treatment group (DCM-TP). After successful modeling, serum glucose, cholesterol, and triglyceride levels were determined; cardiac structure and function were inspected by ultrasonic cardiography; myocardial pathology was examined by staining with hematoxylin-eosin; transmission electron microscopy was used to observe the morphology and quantity of autophagosomes; and expression levels of autophagy-related proteins LC3-II, SQSTM1/p62, and Beclin-1 were determined by Western blotting.@*RESULTS@#Compared to the NC group, the OB group had normal blood glucose and a high level of blood lipids; both blood glucose and lipids were increased in the DCM group; ultrasonic cardiograms showed that the fraction shortening was reduced in the DCM group. However, these were improved significantly in the DCM-TP group. Hematoxylin-eosin staining showed disordered cardiomyocytes and hypertrophy in the DCM group; however, no differences were found among the remaining groups. Transmission electron microscopy revealed that the numbers of autophagosomes in the DCM and OB-TP groups were obviously increased compared to the NC and OB groups; the number of autophagosomes in the DCM-TP group was reduced. Western blotting showed that the expression of LC3-II/I and Beclin-1 increased obviously, whereas the expression of SQSTM1/p62 was decreased in the DCM and OB-TP groups (P<0.05).@*CONCLUSIONS@#Tea polyphenols had an effect on diabetic cardiomyopathy in rat cardiac function and may alter the levels of autophagy to improve glucose and lipid metabolism in diabetes.


Subject(s)
Animals , Autophagy , Beclin-1 , Blood Glucose , Body Weight , Diabetic Cardiomyopathies , Drug Therapy , Pathology , Lipids , Blood , Male , Myocardium , Pathology , Polyphenols , Pharmacology , Rats , Rats, Sprague-Dawley , Tea , Chemistry
14.
Article in Chinese | WPRIM | ID: wpr-771695

ABSTRACT

To explore the protective effect of naringin(Nar) on the injury of myocardium tissues induced by streptozotocin(STZ) in diabetic rats and the relationship with oxidative stress and endoplasmic reticulum stress(ERS), the male SD rats were intraperitoneally injected with streptozotocin(STZ, 60 mg·kg⁻¹) to establish the diabetic rat model and then randomly divided into the type 1 diabetic rat group(T1DR), the low-dose Nar group(Nar25), the middle-dose Nar group(Nar50) and the high-dose Nar group(Nar100). The normal rats were designed as control group(Con). Nar25, Nar50, Nar100 groups were orally administered with Nar at the doses of 25.0, 50.0, 100.0 mg·kg⁻¹ per day, respectively, while the normal group and the T1DR group were orally administered with saline. At the 8th week after treatment, fasting plasma glucose and heart mass index were measured. The pathological changes in myocardial tissues were observed by microscope. The cardiac malondialdehyde(MDA) level and superoxide dismutase(SOD) activities were measured. The gene and protein expressions of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), cysteinyl aspartate-specific proteinase 12(caspase 12) were detected by qRT-PCR and Western blot. According to the results, compared with control group, the myocardial structure was damaged, the content of MDA was increased, while the activities of SOD were decreased(<0.05) in T1DR group. GRP78, CHOP and caspase 12 mRNA and protein expressions were increased significantly in T1DR group(<0.05, <0.01). Compared with T1DR group, myocardial structure damage was alleviated in Nar treatment group. The content of MDA was decreased, while the activities of SOD were increased significantly. The mRNA and protein expressions of GRP78, CHOP and caspase 12 were increased, especially in middle and high-dose groups(<0.05, <0.01). After treatment with Nar for 8 weeks, myocardial structure damage was obviously alleviated in Nar treatment groups. The content of MDA was decreased, while the activities of SOD were increased significantly in myocardial tissues. The mRNA and protein expressions of GRP78, CHOP and caspase 12 were increased, especially in middle and high-dose groups(<0.05, <0.01). The findings suggest that Nar may protect myocardium in diabetic rats by reducing mitochondrial oxidative stress injuries and inhibiting the ERS-mediated cell apoptosis pathway.


Subject(s)
Animals , Apoptosis , Cardiotonic Agents , Pharmacology , Caspase 12 , Metabolism , Diabetes Mellitus, Experimental , Diabetic Cardiomyopathies , Drug Therapy , Endoplasmic Reticulum Stress , Flavanones , Pharmacology , Heat-Shock Proteins , Metabolism , Male , Malondialdehyde , Metabolism , Oxidative Stress , Rats , Rats, Sprague-Dawley , Superoxide Dismutase , Metabolism , Transcription Factor CHOP , Metabolism
15.
Article in Chinese | WPRIM | ID: wpr-776430

ABSTRACT

Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy, myocardial fibrosis and diastolic dysfunction, which are uncorrelated with underlying coronary artery disease or hypertension. As an important metabolic organelle, mitochondria directly involve the process of cell growth, proliferation, signal transduction, apoptosis and so on. Recent studies have demonstrated a close correlation between the mitochondrial dysfunction and the pathogenesis of diabetic cardiomyopathy. The underlying effects of mitochondrial dysfunction in the progress of diabetic cardiomyopathy involve disturbed metabolism, oxidative stress, defective calcium handling, mitochondrial uncoupling, apoptosis, imbalance of mitochondrial quality control and regulation of MicroRNAs. Traditional Chinese medicines have been widely applied in clinic. Nowadays, more and more herbs of extracts of traditional Chinese medicines have been proved to ameliorate diabetic myocardial injury. Because the improvement of mitochondrial dysfunction has emerged as a promising therapeutic strategy, this review summarizes these effects of mitochondrial dysfunction in diabetic cardiomyopathy, and discusses the intervention studies of traditional Chinese medicine in the field, in expectation to provide new ideas for DCM prevention and treatment.


Subject(s)
Diabetic Cardiomyopathies , Drug Therapy , Pathology , Drugs, Chinese Herbal , Therapeutic Uses , Humans , Medicine, Chinese Traditional , Mitochondria , Pathology , Myocardium
16.
Rev. urug. cardiol ; 32(3): 264-276, dic. 2017. tab
Article in Spanish | LILACS | ID: biblio-903594

ABSTRACT

La enfermedad coronaria, la hipertensión arterial y la diabetes son factores de riesgo independientes para el desarrollo de insuficiencia cardíaca y muerte. La cardiomiopatía diabética (CMD) es una de las etiologías frecuentes de cardiopatía en pacientes con diabetes tipo 1 y tipo 2. Si bien se suele plantear la CMD como la causa de la cardiopatía cuando se excluyen la hipertensión arterial, las valvulopatías y la enfermedad arterial coronaria aterotrombótica, estas coexisten con frecuencia e incluso también con la neuropatía autónoma cardiovascular. En los pacientes con CMD se puede demostrar mediante tests serológicos y por imagen alteraciones a nivel molecular, metabólico, mitocondrial, celular y tisular con infiltración grasa del músculo cardíaco, vinculadas a hiperglicemia, hiperinsulinemia y resistencia a la insulina, así como a lipotoxicidad por ácidos grasos libres, que son responsables del desarrollo de la CMD. Esta entidad primero determina disfunción diastólica del ventrículo izquierdo, más tarde disfunción sistólica e insuficiencia cardíaca. Se diagnostica mediante estudios serológicos de marcadores biológicos múltiples y por técnicas de imagen que evidencian la disfunción ventricular y mejoran la predicción pronóstica de enfermedad cardiovascular en diabéticos. En base a dichas pruebas se ha propuesto una clasificación por estadios o fenotipos clínicos de la CMD, que apunta a su diagnóstico precoz. Puede ser asintomática o ser responsable de síntomas y manifestaciones severas tales como insuficiencia cardíaca, arritmias y muerte súbita. Se puede asociar a hipertensión arterial, a enfermedad coronaria, a otras manifestaciones de microangiopatía y macroangiopatía aterotrombótica y a mortalidad cardiovascular. La prevención y el tratamiento intensivo multifactorial y personalizado de la diabetes, de todas sus alteraciones metabólicas y de la cardiopatía, mejoran la calidad y prolongan la vida. Se espera que investigaciones recientes, en proceso y futuras, determinen portentosos avances en la prevención y en el tratamiento de la CMD, que constituye una de las serias amenazas a la salud de la humanidad.


Coronary heart disease, hypertension and diabetes mellitus are independent risk factors for heart failure and death. Diabetic cardiomyopathy (DCM) is one of the common etiologies of cardiac disease in patients with diabetes type 1 or 2. Although DCM is often considered as the cause of heart disease when arterial hypertension, valvulopathies and atherothrombotic coronary artery are excluded, they coexist frequently, as well as with cardiovascular neuropathy. In patients with DCM, serological and imaging tests can show alterations at the molecular, metabolic, mitochondrial, cellular and tissue levels with fatty infiltration of the heart muscle, linked to hyperglycemia, hyperinsulinemia, insulin resistance, and lipotoxicity by fatty free acids, which are responsible for the development of the cardiomyopathy. The DCM first determines left ventricular diastolic dysfunction, later systolic dysfunction and heart failure. It is diagnosed by serological tests of multiple biological markers and by imaging tests that demonstrate ventricular dysfunction and improve the prognostic prediction of cardiovascular disease in diabetics. Based on these tests, a classification by stages or clinical phenotypes of DCM, which aims at its early diagnosis, has been proposed. It can be asymptomatic or be responsible for symptoms and severe manifestations such as heart failure, arrhythmias and sudden death, and may associate hypertension, coronary disease, other manifestations of microangiopathy and atherothrombotic macroangiopathy and cardiovascular mortality. The prevention and intensive multifactorial and personalized treatment of diabetes and all its metabolic and cardiac alterations, improve quality and prolong life. It is expected that ongoing and future research will determine breakthroughs in the prevention and treatment of DCM, which is one of the serious threats to the health of mankind.


Subject(s)
Humans , Diabetes Mellitus, Type 2/complications , Diabetic Cardiomyopathies/diagnosis , Diabetic Cardiomyopathies/physiopathology , Diabetic Cardiomyopathies/therapy , Diagnostic Techniques and Procedures , Diabetes Mellitus, Type 1/complications
17.
Arch. cardiol. Méx ; 87(4): 278-285, oct.-dic. 2017. tab, graf
Article in English | LILACS | ID: biblio-887537

ABSTRACT

Abstract: Objectives: To establish a relationship between global longitudinal strain (GLS) and Galectin-3 in pre-clinical heart failure in diabetic patients. Galectin-3 is a biomarker in heart failure with depressed ejection fraction (HFdEF). The hypothesis is presented that Galectin-3 is related to GLS and can detect left ventricular dysfunction in heart failure with preserved ejection fraction. Methods: Galectin-3 and GLS were measured in 121 asymptomatic individuals: 14 diabetics with mild depressed ejection fraction (mdEF) (LVEF 47.0 ± 6.9); 76 diabetics with preserved ejection fraction (LVEF 61 ± 5.5), and 31 controls (61.7 ± 5.1). Results: Galectin-3 was elevated in all diabetics vs controls (3.46 ± 1.36 ng/ml vs 2.78 ± 0.91 ng/ml; p = .003). It was also elevated in mdEF (3.76 ± 1.12 ng/ml vs 2.78 ± 0.9 ng/ml; p = .009) and pEF subjects (3.41 ± 1.40 ng/ml vs 2.78 ± 0.9 ng/ml; p = .058), respectively, vs controls. No difference in Gal-3 was found between diabetic groups (p = .603). Diabetics had lower GLS than controls (-18.5 ± 3.9 vs -20 ± 2.6; p = .022). Diabetics with mdEF had lower GLS than those with pEF (-13.3 ± 3.41 vs -19 ± 3.2; P<.001). There was no difference in GLS with pEF compared to controls (-19.4 ± 3.2 vs -20 ± 2.6; p = .70). Conclusions: Galectin-3 is elevated in diabetic patients with mdEF, and is associated with a diminished GLS. GLS could be an early marker of left ventricular dysfunction as well as evidence of diabetic cardiomyopathy.


Resumen: Objetivos: Establecer una asociación entre deformación longitudinal global (DLG) y galectina-3 en insuficiencia cardiaca preclínica en pacientes diabéticos. Galectina-3 es un biomarcador en insuficiencia cardiaca con fracción de eyección deprimida. Nuestra hipótesis es que la DLG y galectina-3 correlacionan y pueden detectar disfunción ventricular en insuficiencia cardiaca con FEVI preservada. Métodos: Se midieron galectina-3 y DLG en 121 individuos asintomáticos: 14 diabéticos con FEVI deprimida leve (FEdl) (FEVI 47 ± 6.9); 76 diabéticos con FEVI preservada (FEp) (FEVI 61 ± 5.5) y 31 sujetos controles (FEVI 61.7 ± 5.1). Resultados: Galectina-3 se encontró elevada en todos los diabéticos vs controles (3.46 ± 1.36 ng/ml vs 2.78 ± 0.91 ng/ml; p = 0.003). Está elevada en sujetos con FEdl (3.76 ± 1.12 vs 2.78 ± 0.9 vs ng/ml p = 0.009) y FEp (3.41 ± 1.40 vs 2.78 ± 0.9 ng/ml p = 0.058), respectivamente vs controles; no encontramos diferencia en galectina-3 en ambos grupos de diabéticos (p = 0.603). Los diabéticos tienen menor DLG que los controles (-18.5 ± 3.9 vs -20 ± 2.6; p = 0.022). Los diabéticos con FEdl tienen DLG más disminuida que aquellos con FEp (-13.3 ± 3.41 vs -19 ± 3.2; p < 0.001). No existe diferencia en DLG con FEp y controles (-19.4 ± 3.2 vs -20 ± 2.6; p = 0.70). Conclusiones: Galectina-3 está elevada en diabéticos con FEdl y correlaciona DLG disminuida. DLG podría ser un marcador temprano de disfunción ventricular y evidencia en miocardiopatía diabética.


Subject(s)
Humans , Male , Female , Middle Aged , Stroke Volume , Galectin 3/blood , Diabetic Cardiomyopathies/physiopathology , Diabetic Cardiomyopathies/blood , Blood Proteins , Echocardiography , Biomarkers/blood , Galectins , Diabetic Cardiomyopathies/diagnostic imaging
18.
Arq. bras. cardiol ; 109(6,supl.1): 1-31, dez. 2017. tab
Article in Portuguese | LILACS | ID: biblio-887990

ABSTRACT

Resumo Fundamentação: desde o primeiro posicionamento da Sociedade Brasileira de Diabetes (SBD) sobre diabetes e prevenção cardiovascular, em 2014,1 importantes estudos têm sido publicados na área de prevenção cardiovascular e tratamento do diabetes,2 os quais contribuíram para a evolução na prevenção primária e secundária nos pacientes com diabetes. Ferramentas de estratificação de risco mais precisas, novos fármacos hipolipemiantes e novos antidiabéticos com efeitos cardiovasculares e redução da mortalidade, são parte desta nova abordagem para os pacientes com diabetes. O reconhecimento de que o diabetes é uma doença heterogênea foi fundamental, sendo claramente demonstrado que nem todos os pacientes diabéticos pertencem a categorias de risco alto ou muito alto. Um porcentual elevado é composto por pacientes jovens, sem os fatores de risco clássicos, os quais podem ser classificados adequadamente em categorias de risco intermediário ou mesmo em baixo risco cardiovascular. O presente posicionamento revisa as melhores evidências atualmente disponíveis e propõe uma abordagem prática, baseada em risco, para o tratamento de pacientes com diabetes. Estruturação: perante este desafio e reconhecendo a natureza multifacetada da doença, a SBD uniu-se à Sociedade Brasileira de Cardiologia (SBC) e à Sociedade Brasileira de Endocrinologia e Metabolismo (SBEM), e formou um painel de especialistas, constituído por 28 cardiologistas e endocrinologistas, para revisar as melhores evidências disponíveis e elaborar uma diretriz contendo recomendações práticas para a estratificação de risco e prevenção da Doença Cardiovascular (DVC) no Diabetes Melito (DM). As principais inovações incluem: (1) considerações do impacto de novos hipolipemiantes e das novas medicações antidiabéticas no risco cardiovascular; (2) uma abordagem prática, baseada em fator de risco, para orientar o uso das estatinas, incluindo novas definições das metas da Lipoproteína de Baixa Densidade-colesterol (LDL-colesterol) e colesterol não Lipoproteína de Alta Densidade HDL; (3) uma abordagem baseada em evidências, para avaliar a isquemia miocárdica silenciosa (IMS) e a aterosclerose subclínica em pacientes com diabetes; (4) as abordagens mais atuais para o tratamento da hipertensão; e (5) recomendação de atualizações para o uso de terapia antiplaquetária. Esperamos que esta diretriz auxilie os médicos no cuidado dedicado aos pacientes com diabetes. Métodos: inicialmente, os membros do painel foram divididos em sete subcomitês para definirem os tópicos principais que necessitavam de uma posição atualizada das sociedades. Os membros do painel pesquisaram e buscaram no PubMed estudos clínicos randomizados e metanálises de estudos clínicos e estudos observacionais de boa qualidade, publicados entre 1997 e 2017, usando termos MeSH: [diabetes], [diabetes tipo 2], [doença cardiovascular], [estratificação de risco cardiovascular] [doença arterial coronária], [rastreamento], [isquemia silenciosa], [estatinas], [hipertensão], [ácido acetilsalicílico]. Estudos observacionais de baixa qualidade, metanálises com alta heterogeneidade e estudos transversais não foram incluídos, embora talvez tenham impactado no Nível de Evidência indicado. A opinião de especialistas foi usada quando os resultados das buscas não eram satisfatórios para um item específico. É importante salientar que este posicionamento não teve a intenção de incluir uma revisão sistemática rigorosa. Um manuscrito preliminar, destacando recomendações de graus e níveis de evidência (Quadro 1), foi esboçado. Este passo levou a várias discussões entre os membros dos subcomitês, que revisaram os achados e fizeram novas sugestões. O manuscrito foi, então, revisto pelo autor líder, encarregado da padronização do texto e da inclusão de pequenas alterações, sendo submetido à apreciação mais detalhada pelos membros dos comitês, buscando uma posição de consenso. Depois desta fase, o manuscrito foi enviado para a banca editorial e edição final, sendo encaminhado para publicação. Quadro 1 Graus de recomendações e níveis de evidências adotados nesta revisão Grau de recomendação Classe I A evidência é conclusiva ou, se não, existe consenso de que o procedimento ou tratamento é seguro e eficaz Classe II Há evidências contraditórias ou opiniões divergentes sobre segurança, eficácia, ou utilidade do tratamento ou procedimento Classe IIa As opiniões são favoráveis ao tratamento ou procedimento. A maioria dos especialistas aprova Classe IIb A eficácia é bem menos estabelecida, e as opiniões são divergentes Classe III Há evidências ou consenso de que o tratamento ou procedimento não é útil, eficaz, ou pode ser prejudicial Níveis de Evidência A Múltiplos estudos clínicos randomizados concordantes e bem elaborados ou metanálises robustas de estudos clínicos randomizados B Dados de metanálises menos robustas, um único estudo clínico randomizado ou estudos observacionais C Opinião dos especialistas


Subject(s)
Humans , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Evidence-Based Medicine/standards , Diabetic Cardiomyopathies/prevention & control , Societies, Medical , Brazil , Risk Factors , Risk Assessment , Diabetic Cardiomyopathies/etiology , Hypercholesterolemia/complications , Cholesterol, LDL
19.
Braz. j. med. biol. res ; 50(8): e6204, 2017. tab, graf
Article in English | LILACS | ID: biblio-888983

ABSTRACT

Oxidative stress plays an important role in the development of diabetic cardiomyopathy. In the present study, we determined whether the effect of astragalus polysaccharides (APS) on diabetic cardiomyopathy was associated with its impact on oxidative stress. Streptozotocin (STZ)-induced diabetic mice and heterozygous superoxide dismutase (SOD2+/-) knockout mice were administered APS. The hemodynamics, cardiac ultrastructure, and the apoptosis, necrosis and proliferation of cardiomyocytes were assessed to evaluate the effect of APS on diabetic and oxidative cardiomyopathy. Furthermore, H2O2 formation, oxidative stress/damage, and SOD activity in cardiomyocytes were evaluated to determine the effects of APS on cardiac oxidative stress. APS therapy improved hemodynamics and myocardial ultrastructure with reduced apoptosis/necrosis, and enhanced proliferation in cardiomyocytes from both STZ-induced diabetic mice and heterozygous SOD2+/- knockout mice. In addition, APS therapy reduced H2O2 formation and oxidative stress/damage, and enhanced SOD activity in both groups of mice. Our findings suggest that APS had benefits in diabetic cardiomyopathy, which may be partly associated with its impact on cardiac oxidative stress.


Subject(s)
Animals , Male , Mice , Polysaccharides/therapeutic use , Superoxide Dismutase/genetics , Plant Extracts/therapeutic use , Astragalus Plant/chemistry , Diabetes Mellitus, Experimental/drug therapy , Diabetic Cardiomyopathies/drug therapy , Apoptosis/drug effects , Streptozocin , Mice, Knockout , Oxidative Stress/drug effects , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/ultrastructure , Microscopy, Electron, Transmission , Cell Proliferation/drug effects , Diabetes Mellitus, Experimental/pathology , Diabetic Cardiomyopathies/pathology , Mice, Inbred C57BL
20.
Article in English | WPRIM | ID: wpr-185789

ABSTRACT

BACKGROUND: Cardiac dysfunction in patients with type 1 diabetes (T1D) represents one of the serious complications. To evaluate the cardiac function in children with T1D by conventional echocardiography and tissue Doppler imaging (TDI). METHODS: The study included 40 T1D patients (age between 6 and 16 years) with > 5 years duration of diabetes and 42 healthy control children. The patients were subjected to clinical evaluation and laboratory investigations [glycosylated hemoglobin A1c (HbA1c), serum lipids and lipoproteins]. Conventional echocardiography and TDI were performed to patients and controls. RESULTS: The patients had lower early diastolic filling velocity (E wave) of the tricuspid valve and mitral valves with a p value of (0.000 and 0.006, respectively). TDI revealed that patients had lower S′velocity of the T1D, shorter isovolumic contraction time, longer isovolumic relaxation time and lower E/E′ of the right ventricle than controls (p value 0.002, 0.001, 0.004, 0.003, and 0.016, respectively). The left ventricle (LV)-T1D of the patients was significantly higher (p value 0.02). Twenty eight patients had poor glycemic control without significant differences between them and those with good glycemic control regarding echocardiographic data. Patients with dyslipidemia (13 patients) had higher late diastolic filling velocity of the mitral valve (A) and the lower LV late tissue velocity (A′) (p wave 0.047 and 0.015). No correlation existed between the duration of illness or the level of HbA1c and the echocardiographic parameters. CONCLUSION: Diabetic children have evidence of echocardiographic diastolic dysfunctions. Periodic cardiac evaluation with both conventional and tissue Doppler echocardiography is recommended for early detection of this dysfunction.


Subject(s)
Adolescent , Child , Diabetic Cardiomyopathies , Dyslipidemias , Echocardiography , Echocardiography, Doppler , Heart Ventricles , Humans , Mitral Valve , Relaxation , Tricuspid Valve
SELECTION OF CITATIONS
SEARCH DETAIL