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1.
Hipertens. riesgo vasc ; 36(3): 145-161, jul.-sept. 2019. ilus, graf, tab
Artigo em Espanhol | IBECS | ID: ibc-183954

RESUMO

La enfermedad cardiovascular (ECV) es la causa más frecuente de mortalidad en pacientes con diabetes tipo2 (DM2). En los últimos años, varios fármacos antihiperglucemiantes pertenecientes a dos familias terapéuticas, agonistas del receptor de GLP-1 (arGLP-1) e inhibidores del co-transportador sodio-glucosa tipo2 (iSGLT-2), han demostrado una reducción de la morbimortalidad cardiovascular (CV) en pacientes con DM2 y alto riesgo CV. Los iSGLT-2, a diferencia de los arGLP-1, también disminuyen el riesgo de hospitalización por insuficiencia cardiaca. Ambos grupos terapéuticos reducen la progresión de la enfermedad renal diabética (ERD). El mecanismo cardioprotector de los iSGLT-2 parece ser predominantemente hemodinámico y de aparición precoz, mientras que el de los arGLP-1 es fundamentalmente anti-aterosclerótico y de lenta instauración. En el momento actual diversas sociedades científicas recomiendan el uso preferente de arGLP-1 e iSGLT-2 con beneficio CV demostrado en los pacientes con DM2 y ECV o ERD


Cardiovascular (CV) disease is the most common cause of mortality in patients with type2 diabetes (T2DM). In recent years, several glucose-lowering drugs from two therapeutic families, GLP-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter type 2 inhibitors (SGLT-2i), have shown a reduction in CV morbidity and mortality in patients with T2DM and high CV risk. SGLT-2i, unlike GLP-1 RAs, also reduce the risk of hospital admission due to heart failure. Both therapeutic groups reduce the progression of diabetic kidney disease (DKD). The cardioprotective mechanism of SGLT-2i appears to be predominantly haemodynamic and shows an early onset, while that of GLP-1 RAs is mostly anti-atherosclerotic with a slow and progressive onset. At present, several scientific societies recommend the preferential use of GLP-1 RAs and SGLT-2i, with demonstrated CV benefit in patients with T2DM and cardiovascular disease or DKD


Assuntos
Humanos , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Indicadores de Morbimortalidade , Cardiotônicos/uso terapêutico , Rosiglitazona/uso terapêutico
2.
Br J Anaesth ; 123(4): 439-449, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31383364

RESUMO

BACKGROUND: Nerve growth factor (NGF) has been implicated in hyperalgesia by sensitising nociceptors. A role for NGF in modulating myocardial injury through ischaemic nociceptive signalling is plausible. We examined whether inhibition of spinal NGF attenuates myocardial ischaemia-reperfusion injury and explored the underlying mechanisms. METHODS: In adult rats, lentivirus-mediated short-hairpin RNA targeted at reducing NGF gene expression (NGF-shRNA) or a transient receptor potential vanilloid 1 (TRPV1) antagonist (capsazepine) was injected intrathecally before myocardial ischaemia-reperfusion. Infarct size (expressed as the ratio of area at risk) and risk of arrhythmias were quantified. Whole-cell clamp patch electrophysiology was used to record capsaicin currents in primary dorsal root ganglion neurones. The co-expression of substance P (SP) and calcitonin gene-related peptide (CGRP), plus activation of TRPV1, protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) were also quantified. RESULTS: NGF levels increased by 2.95 (0.34)-fold in dorsal root ganglion and 2.12 (0.27)-fold in spinal cord after myocardial ischaemia-reperfusion injury. Intrathecal injection of NGF-shRNA reduced infarct area at risk from 0.58 (0.02) to 0.37 (0.02) (P<0.01) and reduced arrhythmia score from 3.67 (0.33) to 1.67 (0.33) (P<0.01). Intrathecal capsazepine was similarly cardioprotective. NGF-shRNA suppressed expression of SP/CGRP and activation of Akt/ERK and TRPV1 in spinal cord. NGF increased capsaicin current amplitude from 144 (42) to 840 (132) pA (P<0.05), which was blocked by the TRPV1 antagonist 5'-iodoresiniferatoxin. Exogenous NGF enhanced capsaicin-induced Akt/ERK and TRPV1 activation in PC12 neuroendocrine tumour cells in culture. CONCLUSIONS: Spinal NGF contributes to myocardial ischaemia-reperfusion injury by mediating nociceptive signal transmission.


Assuntos
Terapia Genética/métodos , Lentivirus/genética , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Fator de Crescimento Neural/genética , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/uso terapêutico , Animais , Arritmias Cardíacas/prevenção & controle , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Cardiotônicos/administração & dosagem , Cardiotônicos/uso terapêutico , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Injeções Espinhais , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/prevenção & controle , Fator de Crescimento Neural/biossíntese , Células PC12 , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/metabolismo
3.
Life Sci ; 234: 116773, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31422095

RESUMO

AIMS: NLRP3 inflammasome activation is essential for the development and prognosis of diabetic cardiomyopathy (DCM). The anti-aging protein Klotho is suggested to modulate tissue inflammatory responses. The aim of the present study was to examine the protective effects of Klotho on DCM. MAIN METHODS: A streptozotocin-induced diabetes mouse model was established to assess the effects of Klotho in vivo, which was administered for 12 weeks. The characteristics of type 1 DCM were evaluated by general status, echocardiography, and histopathology. The expression of associated factors was determined by RT-qPCR and western blotting. Parallel experiments to determine the molecular mechanism through which Klotho prevents DCM were performed using H9C2 cells exposed to high glucose (35 mM). KEY FINDINGS: Diabetes-induced increases in serum creatine kinase-muscle/brain and lactate dehydrogenase levels, cardiac fibrosis, cardiomyocyte apoptosis, and cardiac dysfunction were ameliorated by Klotho. Additionally, Klotho suppressed TXNIP expression, NLRP3 inflammasome activation, and expression of the inflammatory cytokines tumor necrosis factor ɑ, interleukin-1ß, and interleukin-18 in vivo. In high glucose-cultured cardiomyocytes, Klotho and N-acetylcysteine significantly downregulated intracellular reactive oxygen species generation and TXNIP/NLRP3 inflammasome activation. Pretreatment of H9C2 cells with NLRP3 siRNA or Klotho prevented high glucose-induced inflammation and apoptosis in H9C2 cells. SIGNIFICANCE: Our results demonstrate that the protective effect of Klotho on diabetes-induced cardiac injury is associated with inhibition of the NLRP3 inflammasome pathway, suggesting its therapeutic potential for DCM.


Assuntos
Diabetes Mellitus Experimental/imunologia , Cardiomiopatias Diabéticas/imunologia , Glucuronidase/imunologia , Inflamassomos/imunologia , Inflamação/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Animais , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/uso terapêutico , Cardiotônicos/imunologia , Cardiotônicos/uso terapêutico , Linhagem Celular , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/patologia , Glucuronidase/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/patologia , Masculino , Camundongos Endogâmicos C57BL , Ratos , Espécies Reativas de Oxigênio/imunologia
4.
Emerg Med Clin North Am ; 37(3): 493-509, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31262417

RESUMO

Although cardiogenic shock is uncommon in the emergency department, it is associated with high mortality. Most cardiogenic shock is caused by ischemia, but nonischemic etiologies are essential to recognize. Clinicians should optimize preload, contractility, and afterload. Volume-responsive patients should be resuscitated in small aliquots, although some patients may require diuresis to improve cardiac output. Vasopressors are important to restore end-organ perfusion, and inotropes improve contractility. Intubation and positive pressure ventilation impact hemodynamics, which, depending on volume status, may be beneficial or deleterious. Knowing indications for mechanical circulatory support is important for timely consultation or transfer as indicated.


Assuntos
Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Algoritmos , Antiarrítmicos/uso terapêutico , Cardiotônicos/uso terapêutico , Cateterismo , Ecocardiografia , Eletrocardiografia , Medicina de Emergência , Cardiopatias/complicações , Cardiopatias/diagnóstico , Cardiopatias/terapia , Humanos , Ácido Láctico/sangue , Anamnese , Monitorização Fisiológica , Peptídeos Natriuréticos/sangue , Exame Físico , Sistemas Automatizados de Assistência Junto ao Leito , Troponina/sangue , Vasoconstritores/uso terapêutico
5.
Cell Mol Life Sci ; 76(20): 4103-4115, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31250032

RESUMO

Cardiovascular diseases (CVDs) are among the leading threats to human health. The advanced glycation end product (AGE) and receptor for AGE (RAGE) signaling pathway regulates the pathogenesis of CVDs, through its effects on arterial stiffness, atherosclerosis, mitochondrial dysfunction, oxidative stress, calcium homeostasis, and cytoskeletal function. Targeting the AGE/RAGE pathway is a potential therapeutic strategy for ameliorating CVDs. Vitamin D has several beneficial effects on the cardiovascular system. Experimental findings have shown that vitamin D regulates AGE/RAGE signaling and its downstream effects. This article provides a comprehensive review of the mechanistic insights into AGE/RAGE involvement in CVDs and the modulation of the AGE/RAGE signaling pathways by vitamin D.


Assuntos
Cardiomiopatias Diabéticas/prevenção & controle , Produtos Finais de Glicação Avançada/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocardite/prevenção & controle , Receptor para Produtos Finais de Glicação Avançada/genética , Vitamina D/uso terapêutico , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/ultraestrutura , Animais , Cálcio/metabolismo , Cardiotônicos/uso terapêutico , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/patologia , Regulação da Expressão Gênica , Produtos Finais de Glicação Avançada/sangue , Guanidinas/uso terapêutico , Humanos , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Miocardite/sangue , Miocardite/genética , Miocardite/patologia , Estresse Oxidativo/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/sangue , Transdução de Sinais , Tiazóis/uso terapêutico , Rigidez Vascular/efeitos dos fármacos , Vitamina D/sangue
6.
Pediatr Cardiol ; 40(6): 1171-1174, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177303

RESUMO

The objective of this study was to describe a cohort of patients with clinical myocarditis and normal left ventricular (LV) systolic function on admission. A retrospective chart review at seven tertiary pediatric hospitals identified patients aged < 19 years admitted with an ICD-9 code of myocarditis between 2008 and 2012. Patients were excluded if admission LV systolic ejection fraction was < 50%, fractional shortening (FS) was < 28% or if the admitting or consulting cardiologist did not suspect myocarditis. A total of 75 patients met inclusion criteria. The median age was 15.5 years with an Interquartile Range (IQR) of 13.6-16.6. 33% were female. Patients presented most commonly with chest pain (75%) and dyspnea (24%). On admission, median B-type natriuretic peptide (BNP) was 132 pg/mL (IQR 57-689) and median troponin I (TnI) was 8.4 ng/mL (IQR 2.0-20.3). Electrocardiogram revealed ST elevation in the majority (55%). Magnetic resonance imaging was obtained on 40%, with 63% of those showing evidence of inflammation. Therapies included inotropic support (15%), mechanical ventilation (12%), antiarrhythmic medications (9%), and Extracorporeal Membrane Oxygenation (5%). Those with poor outcomes were noted to have significantly higher BNP, TnI, and creatine kinase levels on presentation. One patient was transplanted and 35% were discharged on heart failure medications. At one year follow-up one patient had died of unspecified causes, 15% required readmission for cardiac reasons, and 21% continued on heart failure medications. The risk associated with clinical myocarditis in the setting of normal ventricular function at presentation may be higher than previously suspected.


Assuntos
Miocardite/diagnóstico , Função Ventricular Esquerda/fisiologia , Adolescente , Antiarrítmicos/uso terapêutico , Cardiotônicos/uso terapêutico , Dor no Peito/etiologia , Eletrocardiografia , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Humanos , Masculino , Miocardite/mortalidade , Miocardite/terapia , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Troponina I/sangue
8.
EuroIntervention ; 15(7): 586-593, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31147306

RESUMO

AIMS: The haemodynamic effects of primary implantation of an intra-aortic balloon pump (IABP) versus inotropes in decompensated heart failure and low output (DHF-LO), but without an acute coronary syndrome, have not been investigated. We therefore aimed to investigate the effect of primary IABP implantation as compared to inotropes on haemodynamics in DHF-LO with no acute ischaemia. METHODS AND RESULTS: Patients (n=32) with DHF-LO despite IV diuretics were randomised to primary 50 mL IABP or inotropes (INO: enoximone or dobutamine). The primary endpoint was the improvement of organ perfusion assessed by ∆ mixed-venous oxygen saturation (SvO2) at 3 hours; secondary endpoints included ∆ cardiac power output (CPO), NT-proBNP proportional change, cumulative fluid balance and ∆ dyspnoea severity score, all at 48 hours. Data are presented as median (IQR). Patients were 60 (48-69) years old and 72% were male. Baseline SvO2 was 44 (39-53)%. ∆SvO2 was higher in the IABP group (+17 [+9; +24] vs. +5 [+2; +9]%, p<0.05). IABP patients had a higher ∆CPO, a greater relative reduction in NT-proBNP, a more negative cumulative fluid balance, and a greater reduction in dyspnoea severity score. There were no IABP-related serious adverse events (SAEs). Thirty-day mortality was 23% (IABP) vs. 44% (INO). CONCLUSIONS: Primary circulatory support by IABP showed a significant increase in improved organ perfusion assessed by SvO2.


Assuntos
Débito Cardíaco/fisiologia , Cardiotônicos/uso terapêutico , Dobutamina/uso terapêutico , Enoximona/uso terapêutico , Insuficiência Cardíaca/cirurgia , Hemodinâmica/fisiologia , Balão Intra-Aórtico/métodos , Idoso , Débito Cardíaco/efeitos dos fármacos , Feminino , Coração Auxiliar , Hemodinâmica/efeitos dos fármacos , Humanos , Balão Intra-Aórtico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
9.
Cell Mol Life Sci ; 76(20): 3969-3985, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31218451

RESUMO

Cardiovascular diseases represent one of the most important health problems of developed countries. One of the main actors involved in the onset and development of cardiovascular diseases is the increased production of reactive oxygen species that, through lipid peroxidation, protein oxidation and DNA damage, induce oxidative stress and cell death. Basic and clinical research are ongoing to better understand the endogenous antioxidant mechanisms that counteract oxidative stress, which may allow to identify a possible therapeutic targeting/application in the field of stress-dependent cardiovascular pathologies. In this context, increasing attention is paid to the glutathione/glutathione-peroxidase and to the thioredoxin/thioredoxin-reductase systems, among the most potent endogenous antioxidative systems. These key enzymes, belonging to the selenoprotein family, have a well-established function in the regulation of the oxidative cell balance. The aim of the present review was to highlight the role of selenoproteins in cardiovascular diseases, introducing the emerging cardioprotective role of endoplasmic reticulum-resident members and in particular one of them, namely selenoprotein T or SELENOT. Accumulating evidence indicates that the dysfunction of different selenoproteins is involved in the susceptibility to oxidative stress and its associated cardiovascular alterations, such as congestive heart failure, coronary diseases, impaired cardiac structure and function. Some of them are under investigation as useful pathological biomarkers. In addition, SELENOT exhibited intriguing cardioprotective effects by reducing the cardiac ischemic damage, in terms of infarct size and performance. In conclusion, selenoproteins could represent valuable targets to treat and diagnose cardiovascular diseases secondary to oxidative stress, opening a new avenue in the field of related therapeutic strategies.


Assuntos
Cardiotônicos/uso terapêutico , Doenças Cardiovasculares/genética , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Peptídeos/uso terapêutico , Selenocisteína/metabolismo , Selenoproteínas/genética , Animais , Antioxidantes/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/terapia , Regulação da Expressão Gênica , Glutationa Peroxidase/metabolismo , Humanos , Terapia de Alvo Molecular/métodos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Isoformas de Proteínas/agonistas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Selenoproteínas/agonistas , Selenoproteínas/metabolismo , Tiorredoxina Dissulfeto Redutase/metabolismo
10.
Int J Mol Sci ; 20(11)2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31146391

RESUMO

The noble gas helium (He) induces cardioprotection in vivo through unknown molecular mechanisms. He can interact with and modify cellular membranes. Caveolae are cholesterol and sphingolipid-enriched invaginations of the plasma-membrane-containing caveolin (Cav) proteins that are critical in protection of the heart. Mice (C57BL/6J) inhaled either He gas or adjusted room air. Functional measurements were performed in the isolated Langendorff perfused heart at 24 h post He inhalation. Electron paramagnetic resonance spectrometry (EPR) of samples was carried out at 24 h post He inhalation. Immunoblotting was used to detect Cav-1/3 expression in whole-heart tissue, exosomes isolated from platelet free plasma (PFP) and membrane fractions. Additionally, transmission electron microscopy analysis of cardiac tissue and serum function and metabolomic analysis were performed. In contrast to cardioprotection observed in in vivo models, the isolated Langendorff perfused heart revealed no protection after He inhalation. However, levels of Cav-1/3 were reduced 24 h after He inhalation in whole-heart tissue, and Cav-3 was increased in exosomes from PFP. Addition of serum to muscle cells in culture or naïve ventricular tissue increased mitochondrial metabolism without increasing reactive oxygen species generation. Primary and lipid metabolites determined potential changes in ceramide by He exposure. In addition to direct effects on myocardium, He likely induces the release of secreted membrane factors enriched in caveolae. Our results suggest a critical role for such circulating factors in He-induced organ protection.


Assuntos
Cardiotônicos/farmacologia , Caveolinas/metabolismo , Coração/efeitos dos fármacos , Hélio/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Cardiotônicos/uso terapêutico , Cavéolas/efeitos dos fármacos , Cavéolas/metabolismo , Caveolinas/sangue , Caveolinas/genética , Células Cultivadas , Exossomos/efeitos dos fármacos , Exossomos/metabolismo , Hélio/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle
11.
Med. infant ; 26(2): 189-196, Junio 2019. Tab, ilus
Artigo em Espanhol | LILACS | ID: biblio-1021542

RESUMO

La Insuficiencia Cardíaca (IC) es un síndrome clínico que epresenta una de las mayores causas de mobi-mortalidad en pacientes pediátricos. Refleja la incapacidad del corazón para satisfacer las necesidades metabólicas del organismo, incluido el crecimiento y el ejercicio. En el niño la causa más frecuente es la cardiopatía congénita. Otras causas las miocardiopatía, las miocarditis, las arritmias y las causas no cardíacas como: insuficiencia renal, hipertensión arterial, enfermedades pulmonares crónicas, anemia, sepsis, hiper e hipotiroidismo, cardiotoxicidad, etc. Clásicamente el tratamiento estaba dirigido a mejorar la contractilidad y evitar la retención hidrosalina con digital y diuréticos. En la actualidad, dado a la mejor comprensión del mecanismo fisiopatológico, en los últimos años, el tratamiento se centra en el control de los sistemas renina-angiotensina (SRAA) y nervioso simpático. En los casos de IC descompensada que presentan síndrome de bajo gasto cardíaco que no responde a la terapia médica, previo al trasplante cardíaco, está indicado el soporte mecánico (AU)


Heart failure (HF) reflects the inability of the heart to meet the metabolic needs of the body, including growth and exercise. In the child, the most common cause is congenital heart disease. Other causes are cardiomyopathy, myocarditis, arrhythmias, and non-cardiac causes, such as renal failure, high blood pressure, chronic pulmonary diseases, anemia, sepsis, hyper- and hypothyroidism, cardiotoxicity. Classically, the treatment aimed at improving contractility and avoiding salt and fluid retention using digitalis and diuretics. Given the current better understanding of the pathophysiological mechanism, over the past years treatment has focused on the control of renin-angiotensin (RAAS) and sympathetic nervous systems. In cases of decompensated HF with low cardiac output syndrome not responding to medical therapy, prior to cardiac transplantation mechanical support is indicated (AU)


Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/terapia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Cardiotônicos/uso terapêutico , Coração Auxiliar , Agonistas Adrenérgicos beta/uso terapêutico , Diuréticos/uso terapêutico
12.
Rev Assoc Med Bras (1992) ; 65(4): 524-529, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31066804

RESUMO

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.


Assuntos
Cardiomiopatia Dilatada/tratamento farmacológico , Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Simendana/uso terapêutico , Brasil , Cardiomiopatia Dilatada/mortalidade , Tomada de Decisão Clínica , Insuficiência Cardíaca/mortalidade , Humanos , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do Tratamento
13.
Chem Biol Interact ; 308: 20-44, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31067438

RESUMO

Ischemic heart disease (IHD) is a major cause of cardiovascular morbidity and mortality worldwide, which is characterized by an imbalance between cardiac oxygen supply and demand predominantly due to obstruction of coronary arteries. Activation of the innate immune system and the consequent inflammatory response plays a role in the pathogenesis of IHD. Where an excessive inflammatory response may contribute to adverse cardiac remodeling and fibrosis, making inflammation an important therapeutic target for improving outcomes of IHD. While there are many discrepancies in the literature, evidence from both bench and clinical research demonstrate important effects of n-3 polyunsaturated fatty acids (n-3 PUFA), eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA), toward IHD. N-3 PUFAs, and their metabolites, have been demonstrated to modulate various components of the immune system, including regulation of chemokines and cytokines, leukocyte chemotaxis and inflammasome formation. In this article, we provide an overview of the role the innate immune system has in IHD and focus on the immunomodulatory effects of n-3 PUFAs and their biologically active metabolites.


Assuntos
Cardiotônicos/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Imunidade Inata , Isquemia Miocárdica/tratamento farmacológico , Alarminas/metabolismo , Cardiotônicos/farmacologia , Membrana Celular/química , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Ciclo-Oxigenase 1/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Humanos , Imunidade Inata/efeitos dos fármacos , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Isquemia Miocárdica/imunologia , Isquemia Miocárdica/patologia , Proteína-Lisina 6-Oxidase/metabolismo
14.
Biomed Res Int ; 2019: 6803943, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31139646

RESUMO

During myocardial infarction, quickly opening the occluded coronary artery is a major method to save the ischemic myocardium. However, it also induces reperfusion injury, resulting in a poor prognosis. Alleviating the reperfusion injury improves the prognosis of the patients. Dihydromyricetin (DHM), a major component in the Ampelopsis grossedentata, has numerous biological functions. This study aims to clarify the effects of DHM under the ischemia/reperfusion (I/R) condition. We elucidated the role of Sirt3 in the cardiomyocyte response to DHM based on the hearts and primary cardiomyocytes. Cardiac function, mitochondrial biogenesis, and infarct areas were examined in the different groups. We performed Western blotting to detect protein expression levels after treatments. In an in vitro study, primary cardiomyocytes were treated with Hypoxia/Reoxygenation (H/R) to simulate the I/R. DHM reduced the infarct area and improved cardiac function. Furthermore, mitochondrial dysfunction was alleviated after DHM treatment. Moreover, DHM alleviated oxidative stress indicated by decreased ROS and MnSOD. However, the beneficial function of DHM was abolished after removing the Sirt3. On the other hand, the mitochondrial function was improved after DHM intervention in vitro study. Interestingly, Sirt3 downregulation inhibited the beneficial function of DHM. Therefore, the advantages of DHM are involved in the improvement of mitochondrial function and decreased oxidative stress through the upregulation of Sirt3. DHM offers a promising therapeutic avenue for better outcome in the patients with cardiac I/R injury.


Assuntos
Flavonóis/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Sirtuína 3/metabolismo , Animais , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Células Cultivadas , Proteínas de Ligação a DNA/metabolismo , Flavonóis/farmacologia , Proteínas de Grupo de Alta Mobilidade/metabolismo , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Oxigênio
15.
Chem Commun (Camb) ; 55(44): 6193-6196, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31070620

RESUMO

Hydrogen sulfide (H2S) is an important signaling molecule with promising protective effects in many physiological and pathological processes. However, the study of H2S has been impeded by the lack of appropriate H2S donors that could mimic its slow-releasing process in vivo. Herein, we report the rational design, synthesis, and biological evaluation of a series of thioester-based H2S donors. These cysteine-activated H2S donors release H2S in a slow and controllable manner. Most of the donors comprising an allyl moiety showed significant cytoprotective effects in H9c2 cellular models of oxidative damage. The most potent donor 5e decreased the mitochondrial membrane potential (MMP) loss and lactate dehydrogenase (LDH) release in H2O2-stimulated H9c2 cells. More importantly, donor 5e exhibited a potent cardioprotective effect in an in vivo myocardial infarction (MI) mouse model by reducing myocardial infarct size and cardiomyocyte apoptosis. Taken together, our studies demonstrated that these new allyl thioesters are potential cardioprotective agents by releasing H2S.


Assuntos
Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Ésteres/química , Sulfeto de Hidrogênio/química , Compostos de Sulfidrila/química , Animais , Linhagem Celular , Modelos Animais de Doenças , Peróxido de Hidrogênio/farmacologia , L-Lactato Desidrogenase/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/metabolismo , Estresse Oxidativo
16.
Biomed Res Int ; 2019: 4303215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119169

RESUMO

Leonurus cardiaca L. (motherwort) is a perennial herb, native to Asia and southeastern Europe, with widespread global occurrence in present days. The plant was historically used as cardiotonic and for treating gynaecological afflictions (such as amenorrhea, dysmenorrhea, menopausal anxiety, or postpartum depression). Although its use in oriental and occidental medicine is relatively well documented, the recent progress registered raises the need for an update of the Medicines Agency assessment report on Leonurus cardiaca L., herba (2010). The current study presents the progress made within the 2010-2018 timeframe regarding the potential applications and scientific evidences supporting the traditional use of motherwort, in the same time suggesting future research opportunities.


Assuntos
Cardiotônicos/uso terapêutico , Leonurus/química , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Amenorreia/tratamento farmacológico , Ásia , Cardiotônicos/química , Dismenorreia/tratamento farmacológico , Europa (Continente) , Feminino , Humanos , Menopausa/efeitos dos fármacos , Compostos Fitoquímicos/química , Extratos Vegetais/química
17.
Int J Mol Sci ; 20(6)2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30934608

RESUMO

Despite the availability of several therapies for the management of blood glucose in diabetic patients, most of the treatments do not show benefits on diabetic cardiomyopathy, while others even favor the progression of the disease. New pharmacological targets are needed that might help the management of diabetes and its cardiovascular complications at the same time. GRK2 appears a promising target, given its established role in insulin resistance and in systolic heart failure. Using a custom peptide inhibitor of GRK2, we assessed in vitro in L6 myoblasts the effects of GRK2 inhibition on glucose extraction and insulin signaling. Afterwards, we treated diabetic male mice (db/db) for 2 weeks. Glucose tolerance (IGTT) and insulin sensitivity (ITT) were ameliorated, as was skeletal muscle glucose uptake and insulin signaling. In the heart, at the same time, the GRK2 inhibitor ameliorated inflammatory and cytokine responses, reduced oxidative stress, and corrected patterns of fetal gene expression, typical of diabetic cardiomyopathy. GRK2 inhibition represents a promising therapeutic target for diabetes and its cardiovascular complications.


Assuntos
Cardiotônicos/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Quinase 2 de Receptor Acoplado a Proteína G/antagonistas & inibidores , Hipoglicemiantes/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Transporte Biológico/efeitos dos fármacos , Cardiomegalia/complicações , Cardiomegalia/tratamento farmacológico , Cardiomegalia/patologia , Cardiotônicos/farmacologia , Linhagem Celular , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Glucose/metabolismo , Hipoglicemiantes/farmacologia , Inflamação/patologia , Insulina/metabolismo , Resistência à Insulina , Masculino , Camundongos , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos
18.
Int J Mol Sci ; 20(7)2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30934670

RESUMO

Resveratrol, the phenolic substance isolated initially from Veratrum grandiflorum and richly present in grapes, wine, peanuts, soy, and berries, has been attracting attention of scientists and medical doctors for many decades. Herein, we review its effects on the vascular system. Studies utilizing cell cultures and pre-clinical models showed that resveratrol alleviates oxidative stress and inflammation. Furthermore, resveratrol suppresses vascular smooth muscle cell proliferation, promotes autophagy, and has been investigated in the context of vascular senescence. Pre-clinical models unambiguously demonstrated numerous vasculoprotective effects of resveratrol. In clinical trials, resveratrol moderately diminished systolic blood pressure in hypertensive patients, as well as blood glucose in patients with diabetes mellitus. Yet, open questions remain, as exemplified by a recent report which states that the intake of resveratrol might blunt certain positive effects of exercise in older persons, and further research addressing the framework for long-term use of resveratrol as a food supplement, will stay in demand.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Resveratrol/farmacologia , Animais , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Humanos , Resveratrol/uso terapêutico
19.
Int J Mol Sci ; 20(7)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939728

RESUMO

Dexmedetomidine (DEX), a highly selective alpha2 adrenergic receptor agonist, directly protects hearts against ischemia/reperfusion (I/R) injury. However, the detailed mechanism has not been fully elucidated. We studied differentially expressed mRNAs and miRNAs after DEX administration in rat hearts by comprehensive analysis. Additionally, bioinformatics analysis was applied to explore candidate genes and pathways that might play important roles in DEX-induced cardioprotection. The results of microarray analysis showed that 165 mRNAs and 6 miRNAs were differentially expressed after DEX administration. Through bioinformatics analysis using differentially expressed mRNAs, gene ontology (GO) terms including MAP kinase tyrosine/serine/threonine phosphatase activity and pathways including the p53 pathway were significantly enriched in the down-regulated mRNAs. Dusp1 and Atm were associated with the GO term of MAP kinase tyrosine/serine/threonine phosphatase activity and the p53 pathway, respectively. On the other hand, no significant pathway was found in the target mRNAs of deregulated miRNAs. The results indicated some possible key genes and pathways that seem to be of significance in DEX-induced cardioprotection, although miRNAs seem to be unlikely to contribute to cardioprotection induced by DEX.


Assuntos
Cardiotônicos/farmacologia , Dexmedetomidina/farmacologia , Coração/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/genética , Transcriptoma , Animais , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Cardiotônicos/uso terapêutico , Dexmedetomidina/uso terapêutico , Fosfatase 1 de Especificidade Dupla/genética , Fosfatase 1 de Especificidade Dupla/metabolismo , Perfilação da Expressão Gênica , Sistema de Sinalização das MAP Quinases , Masculino , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Ratos , Ratos Wistar , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
20.
Phytomedicine ; 55: 320-329, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30940361

RESUMO

BACKGROUND: It has been reported that n-butanol extract of Potentilla anserina L (NP) had protective effect against acute myocardial ischemia/reperfusion (I/R) injury in mice. Because of limited phytochemical study on NP, its bioactive compounds and underlying protective mechanisms are largely unclear. PURPOSE: The purpose of this study was to investigate the major bioactive compounds and possible mechanism for the cardioprotective effect of NP on rat with I/R injury. METHODS: We analyzed the phytochemical isolation of NP and identified the structure of compounds, which was elucidated by a combination of spectroscopic analyses. An I/R model was established by I-30 min/R-2 h in Sprage-Dawley rats. The rats were given intragastric administration of NP (49.3, 98.6, and 197.2 mg•kg-1) continuously for 10 days before I/R operation. The morphological changes and apoptosis of cardiomyocytes were observed by H&E staining, Transmission electron microscope and TUNEL staining respectively. The activities or contents of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) in plasma were detected. Apoptosis related factors were also measured by RT-PCR and western blot. In order to discover the underlying mechanism of NP on I/R, we performed proteomic analysis using two-dimensional gel electrophoresis (2D-DIGE) and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/MS) to describe differential proteins expression. Potential target protein resulted from 2D-DIGE coupled to MALDI-TOF/MS analysis were further confirmed by immunohistochemical staining, RT-PCR, and western blot. RESULTS: We isolated and identified 14 compounds, of which 7 compounds belong to triterpenes. Rats pretreated with NP showed a significant increase on the activities of GSH, SOD and CAT, and remarkable decrease on the content of MDA. NP significantly inhibited the apoptosis of cardiomyocyte and decreased the expression of Cyt C and cleaved-caspase-3. Proteomic analysis revealed that alpha B-crystallin (CryAB) might participate in the NP protective effect against I/R. NP enhanced the level of pCryAB Ser59, whereas the expression of CryAB was decreased. CONCLUSION: NP was showed to alleviate I/R injury and inhibit myocardial apoptosis, which might be associated with reduction on oxidative stress and apoptosis. CryAB as a possible target involved in the NP protective effect. This study supplied valuable information to develop novel cardioprotective agents from NP extract.


Assuntos
Cardiotônicos/farmacologia , Isquemia/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miocárdio/metabolismo , Extratos Vegetais/farmacologia , Potentilla/química , Cadeia B de alfa-Cristalina/uso terapêutico , Animais , Cardiotônicos/uso terapêutico , Masculino , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley
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