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1.
Nutrients ; 12(2)2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32098364

RESUMO

Alcoholic-dilated Cardiomyopathy (ACM) is the most prevalent form of ethanol-induced heart damage. Ethanol induces ACM in a dose-dependent manner, independently of nutrition, vitamin, or electrolyte disturbances. It has synergistic effects with other heart risk factors. ACM produces a progressive reduction in myocardial contractility and heart chamber dilatation, leading to heart failure episodes and arrhythmias. Pathologically, ethanol induces myocytolysis, apoptosis, and necrosis of myocytes, with repair mechanisms causing hypertrophy and interstitial fibrosis. Myocyte ethanol targets include changes in membrane composition, receptors, ion channels, intracellular [Ca2+] transients, and structural proteins, and disrupt sarcomere contractility. Cardiac remodeling tries to compensate for this damage, establishing a balance between aggression and defense mechanisms. The final process of ACM is the result of dosage and individual predisposition. The ACM prognosis depends on the degree of persistent ethanol intake. Abstinence is the preferred goal, although controlled drinking may still improve cardiac function. New strategies are addressed to decrease myocyte hypertrophy and interstitial fibrosis and try to improve myocyte regeneration, minimizing ethanol-related cardiac damage. Growth factors and cardiomyokines are relevant molecules that may modify this process. Cardiac transplantation is the final measure in end-stage ACM but is limited to those subjects able to achieve abstinence.

2.
J Pathol ; 248(1): 30-40, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30582148

RESUMO

FGF21 is an endocrine factor that contributes to multiple pathophysiological processes, mainly via its action as a metabolic regulator and cardioprotective agent. Recent studies have shown increased circulating FGF21 levels in hypertensive patients and in mouse models of hypertension. However, the relevance of FGF21 in hypertensive heart disease has not been addressed. Hypertension was induced by treating 4-month old WT and Fgf21-/- mice with angiotensin II (AngII) for 1 week, resulting in a similar increase in blood pressure in both genotypes. Plasma FGF21 levels and expression in heart and liver were significantly increased in hypertensive WT mice relative to controls, an effect that was associated with increased expression levels of ß-klotho specifically in the heart. Fgf21-/- mice developed a greater degree of hypertensive heart disease than WT mice, notably characterized by extensive cardiac dysfunction and fibrosis. In vitro and in vivo studies further showed that FGF21 exerted a marked protective effect against cardiac fibrosis. Finally, left ventricle biopsies from human hypertensive heart donors, especially those developing cardiomyopathy, showed a significant increase in FGF21expression compared with normotensive controls, a finding that was associated with significantly enhanced cardiac hypertrophy and fibrosis. We conclude that during hypertension, both systemic and cardiac-produced FGF21 are induced and act on the heart, protecting it from hypertensive heart disease. Thus, FGF21 acts as key factor in the fibrogenesis associated with hypertensive heart disease. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

7.
Adv Protein Chem Struct Biol ; 108: 227-256, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28427562

RESUMO

Almost 30 years ago, the protein, atrial natriuretic peptide, was identified as a heart-secreted hormone that provides a peripheral signal from the myocardium that communicates to the rest of the organism to modify blood pressure and volume under conditions of heart failure. Since then, additional peripheral factors secreted by the heart, termed cardiokines, have been identified and shown to coordinate this interorgan cross talk. In addition to this interorgan communication, cardiokines also act in an autocrine/paracrine manner to play a role in intercellular communication within the myocardium. This review focuses on the roles of newly emerging cardiokines that are mainly increased in stress-induced cardiac diseases. The potential of these cardiokines as clinical biomarkers for diagnosis and prognosis of cardiac disorders is also discussed.


Assuntos
Cardiopatias/imunologia , Inflamação/imunologia , Miocárdio/imunologia , Ativinas/análise , Ativinas/imunologia , Animais , Biomarcadores/análise , Fatores de Crescimento de Fibroblastos/análise , Fatores de Crescimento de Fibroblastos/imunologia , Folistatina/análise , Folistatina/imunologia , Proteínas Relacionadas à Folistatina/análise , Proteínas Relacionadas à Folistatina/imunologia , Fator 15 de Diferenciação de Crescimento/análise , Fator 15 de Diferenciação de Crescimento/imunologia , Cardiopatias/complicações , Cardiopatias/patologia , Humanos , Inflamação/complicações , Inflamação/patologia , Interleucina-33/análise , Interleucina-33/imunologia , Miocárdio/patologia , Miostatina/análise , Miostatina/imunologia , Comunicação Parácrina , Estresse Fisiológico , Fator de Crescimento Transformador beta/análise , Fator de Crescimento Transformador beta/imunologia
8.
Int J Mol Sci ; 17(10)2016 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-27690014

RESUMO

High-dose alcohol misuse induces multiple noxious cardiac effects, including myocyte hypertrophy and necrosis, interstitial fibrosis, decreased ventricular contraction and ventricle enlargement. These effects produce diastolic and systolic ventricular dysfunction leading to congestive heart failure, arrhythmias and an increased death rate. There are multiple, dose-dependent, synchronic and synergistic mechanisms of alcohol-induced cardiac damage. Ethanol alters membrane permeability and composition, interferes with receptors and intracellular transients, induces oxidative, metabolic and energy damage, decreases protein synthesis, excitation-contraction coupling and increases cell apoptosis. In addition, ethanol decreases myocyte protective and repair mechanisms and their regeneration. Although there are diverse different strategies to directly target alcohol-induced heart damage, they are partially effective, and can only be used as support medication in a multidisciplinary approach. Alcohol abstinence is the preferred goal, but control drinking is useful in alcohol-addicted subjects not able to abstain. Correction of nutrition, ionic and vitamin deficiencies and control of alcohol-related systemic organ damage are compulsory. Recently, several growth factors (myostatin, IGF-1, leptin, ghrelin, miRNA, and ROCK inhibitors) and new cardiomyokines such as FGF21 have been described to regulate cardiac plasticity and decrease cardiac damage, improving cardiac repair mechanisms, and they are promising agents in this field. New potential therapeutic targets aim to control oxidative damage, myocyte hypertrophy, interstitial fibrosis and persistent apoptosis In addition, stem-cell therapy may improve myocyte regeneration. However, these strategies are not yet approved for clinical use.

9.
Rev Esp Salud Publica ; 90: e1-7, 2016 Aug 18.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27535808

RESUMO

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a complex and multifactorial disease. Stressful situations experienced could be related to the presentation of the disease. Few studies have determined which factors could trigger CFS. The main objective of this study was to explore the stressful situations which can be associated with CFS presentation. METHODS: Retrospective observational case-control study with CFS diagnosed patients according to the Fukuda's criteria. Controls were matched to cases by sex, age and educational level with a 1:1 ratio. Participants aged between 18 and 75 years from the province of Lleida. Information was obtained through personal questionnaires. The measure of association was the odds ratio. RESULTS: In total, 77 cases and 77 controls were included. Association found between stressful life events and presentation of disease were pregnancy ORa=31.7 (CI95%:2.2-456.7), spousal abuse ORa= 10.2 (CI95%:1.2-88.4) and mobbing ORa=6.9 (CI95%:1.3-36.9), eating disorders=7.5 (CI95%:1.3-42.1), car accident ORa=5.5 (CI95%:1.7-17 9), economic problems ORa=5.1 (CI95%:2.1-12.6) and changes in sleep habits ORa=2.8 (CI95%:1.1-7.5). CONCLUSIONS: Stressful life events as pregnancy, spousal abuse, mobbing, eating disorders, car accident, economic problems and changes in sleep habits felt by those affected must be taken into consideration when compiling background information related to the onset of Chronic Fatigue Syndrome. Adequate identification of these stressful life events in risk people could contribute to early diagnosis of Chronic Fatigue Syndrome.


Assuntos
Síndrome de Fadiga Crônica/psicologia , Estresse Psicológico/complicações , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Espanha , Estresse Psicológico/diagnóstico , Inquéritos e Questionários , Adulto Jovem
10.
Alcohol Alcohol ; 51(4): 457-64, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26818195

RESUMO

AIM: To determine the detection rates, clinical features, and risk factors for lack of registration of alcohol use in medical patients admitted in European hospitals. METHODS: A point-prevalence, cross-sectional, multicenter survey involving 2100 medical inpatients from 43 hospitals from 8 European countries. Patients were screened for current alcohol use, using standardized questionnaires. Alcohol use recording in medical records was assessed. RESULTS: Of the 2100, more than a half reported alcohol use. Significant differences were shown in the prevalence of drinking and the recording rates of alcohol use among the hospitals and countries involved. Overall, 346 patients (16%) fulfilled criteria for alcohol use disorder. Alcohol use was registered in 909 (43%) of medical records, with quantification in 143 (7%). Multivariate analysis showed that women (OR 1.49), older age patients (OR 1.23), patients from the Northern European countries (OR 4.79) and from hospitals with high local alcohol prevalence (OR 1.59) were more likely to have lack of alcohol use registration in their medical files. CONCLUSIONS: A considerable proportion of medical patients admitted in European hospitals fulfill criteria for alcohol use disorders. These patients are frequently overlooked during hospitalization and not appropriately registered in medical records. Women, older patients, and inpatients from European areas with high local alcohol use prevalence are at higher risk associated with a non-recording of alcohol use.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Hospitais/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Registros Médicos/estatística & dados numéricos , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais , Adulto Jovem
11.
Rev. esp. salud pública ; 90: 0-0, 2016. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-155974

RESUMO

Fundamentos: El síndrome de fatiga crónica (SFC) es una enfermedad compleja y multifactorial. Situaciones estresantes vividas podrían relacionarse con la presentación de la enfermedad. Son pocos los estudios que han determinado estos factores desencadenantes de la presentación del SFC. El objetivo principal del presente estudio fue explorar cuáles pueden ser las Situaciones estresantes asociadas al desencadenamiento del síndrome de fatiga crónica. Métodos: Estudio observacional retrospectivo de casos y controles con pacientes diagnosticados de SFC según los criterios de Fukuda. Los controles se emparejaron con los casos según sexo, edad y nivel de estudios con una razón 1:1. Ambos tenían edades comprendidas entre los 18 y los 75 años y eran residentes en la provincia de Lleida. Se aplicó una tabla de acontecimientos vitales estresantes (AVE). La información se obtuvo mediante encuestas personales. Se realizó regresión logística binaria calculando la odds ratio como medida de asociación. Resultados: Se incluyeron 77 casos y 77 controles. Se evidenció asociación entre acontecimientos vitales estresantes y presentación de la patología, como embarazo con ORa=31,7 (IC95%: 2,2-456,7), maltrato por parte de la pareja ORa=10,2 (IC95%:1,2-88,4), mobbing ORa=6,9 (IC95%:1,3-36,9), trastornos de la alimentación ORa=7,5 (IC95%:1,3-42,1), accidente de tráfico ORa=5,5 (IC95%:1,7-17,9), problemas económicos ORa=5,1 (IC95%:2,1-12,6) y cambios de hábitos de sueño ORa=2,8 (IC95%:1,1-7,5). Conclusiones: Acontecimientos vitales estresantes como el embarazo, el maltrato por parte de la pareja, mobbing, trastornos de alimentación, accidente de tráfico, problemas económicos y cambios de hábitos de sueño percibidos por los afectados, deben tenerse en cuenta al explorar la información relacionada con el desencadenamiento del síndrome de fatiga crónica. Su hallazgo en personas de riesgo podría contribuir a un diagnóstico precoz del síndrome de fatiga crónica (AU)


Background: Chronic Fatigue Syndrome (CFS) is a complex and multifactorial disease. Stressful situations experienced could be related to the presentation of the disease. Few studies have determined which factors could trigger CFS. The main objective of this study was to explore the stressful situations which can be associated with CFS presentation. Methods: Retrospective observational case-control study with CFS diagnosed patients according to the Fukuda’s criteria. Controls were matched to cases by sex, age and educational level with a 1:1 ratio. Participants aged between 18 and 75 years from the province of Lleida. Information was obtained through personal questionnaires. The measure of association was the odds ratio. Results: In total, 77 cases and 77 controls were included. Association found between stressful life events and presentation of disease were pregnancy ORa=31.7 (CI95%:2.2-456.7), spouse abuse ORa=10.2 (CI95%:1.2-88.4) and mobbing ORa=6.9 (CI95%:1.3-36.9), eating disorders=7.5 (CI95%:1.3-42.1), car accident ORa=5.5 (CI95%:1.7-17 9), economic problems ORa=5.1 (CI95%:2.1-12.6) and changes in sleep habits ORa=2.8 (CI95%:1.1-7.5). Conclusions: Stressful life events as pregnancy, spousal abuse, mobbing, eating disorders, car accident, economic problems and changes in sleep habits felt by those affected must be taken into consideration when compiling background information related to the onset of Chronic Fatigue Syndrome. Adequate identification of these stressful life events in risk people could contribute to early diagnosis of Chronic Fatigue Syndrome (AU)


Assuntos
Humanos , Estresse Psicológico/complicações , Síndrome de Fadiga Crônica/etiologia , Diagnóstico Precoce , Modelos Logísticos , Depressão/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia
12.
Nat Rev Cardiol ; 12(10): 576-87, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26099843

RESUMO

The heart and vascular system are susceptible to the harmful effects of alcohol. Alcohol is an active toxin that undergoes widespread diffusion throughout the body, causing multiple synchronous and synergistic effects. Alcohol consumption decreases myocardial contractility and induces arrhythmias and dilated cardiomyopathy, resulting in progressive cardiovascular dysfunction and structural damage. Alcohol, whether at binge doses or a high cumulative lifetime consumption-both of which should be discouraged-is clearly deleterious for the cardiovascular system, increasing the incidence of total and cardiovascular mortality, coronary and peripheral artery disease, heart failure, stroke, hypertension, dyslipidaemia, and diabetes mellitus. However, epidemiological, case-control studies and meta-analyses have shown a U-type bimodal relationship so that low-to-moderate alcohol consumption (particularly of wine or beer) is associated with a decrease in cardiovascular events and mortality, compared with abstention. Potential confounding influences-alcohol-dose quantification, tobacco use, diet, exercise, lifestyle, cancer risk, accidents, and dependence-can affect the results of studies of both low-dose and high-dose alcohol consumption. Mendelian methodological approaches have led to doubts regarding the beneficial cardiovascular effects of alcohol, and the overall balance of beneficial and detrimental effects should be considered when making individual and population-wide recommendations, as reductions in alcohol consumption should provide overall health benefits.


Assuntos
Consumo de Bebidas Alcoólicas , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/prevenção & controle , Consumo de Bebidas Alcoólicas/efeitos adversos , Humanos , Estilo de Vida , Saúde Pública , Fatores de Risco
13.
J Hypertens ; 33(4): 851-8; discussion 859, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25915890

RESUMO

OBJECTIVE: The physiopathological mechanisms implicated in hypertensive heart disease are multi-factorial, including myocyte hypertrophy, apoptosis and myocardial remodelling. In this process, some hormonal and local growth factors have a regulatory influence. The aim of this study was to evaluate the potential role of myostatin and insulin-like growth factor-1 (IGF-1) myocardial expression in the development of hypertensive-induced cardiac damage. METHODS: Samples of human myocardium tissue from organ donors were prospectively collected and classified according to the presence of hypertension, alcohol consumption, other causes of myocardial damage and the presence of structural cardiomyopathy (CMP). Myocardial samples were studied by immunohistochemistry and myostatin, and IGF-1 myocardial expression was evaluated in all the different groups of donors. Hypertensive donors were compared to other groups. RESULTS: A total of 66 heart samples from human donors were collected: 33 donors had no previous or present history of hypertension and 33 donors presented defined hypertension. Donors with hypertension presented higher myocyte cell and nuclear hypertrophy and showed similar myostatin myocardial expression as controls, but lower IGF-1 myocardial expression. Myostatin expression was significantly higher in hypertensive donors with CMP compared to non-hypertensive healthy donors. The presence of CMP of diverse origin (alcoholic, valve and coronary) also significantly increased myostatin myocardial expression. CONCLUSION: The presence of hypertension significantly decreases IGF-1 myocardial expression. Myostatin myocardial expression increases in the presence of structural CMP either of hypertensive or other origin. These effects open the possibility of modulating hypertensive-induced cardiac damage.


Assuntos
Cardiopatias/metabolismo , Hipertensão/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Miocárdio/metabolismo , Miostatina/metabolismo , Adulto , Idoso , Alcoolismo/metabolismo , Apoptose , Estudos de Casos e Controles , Feminino , Expressão Gênica , Cardiopatias/etiologia , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doadores de Tecidos
18.
Regen Med Res ; 1(1): 3, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25984322

RESUMO

BACKGROUND: Alcoholic cardiomyopathy (CMP) is one of the major complications of chronic excessive alcohol consumption. The pathogenic mechanisms implicated are diverse, inducing functional and structural changes in the myocardium. Insulin-like Growth Factor 1 (IGF-1) plays an important role in modulating the cell cycle, and helps the differentiation and proliferation of cardiac tissue inhibiting apoptosis. Experimental studies have suggested the role of IGF-1 in alcohol-induced cardiac damage. The aim of the present study was to determine the effect of chronic alcohol consumption on IGF-1 myocardial expression and to compare this expression in cases of hypertension and other cardiac diseases. METHODS: We studied heart samples from human organ donors: 10 healthy donors, 16 with hypertension, 23 with chronic alcohol consumption and 7 with other causes of cardiac disease. IGF-1 myocardial expression was evaluated with a specific immunohistochemistry assay using a semi-quantitative method. RESULTS: A significant decrease in IGF-1 myocardial expression was observed comparing all the cases included with control donors. This decrease in IGF-1 myocardial expression was significantly lower in the group of donors with chronic alcohol consumption compared to controls. On group evaluation according to the presence of CMP, donors with chronic alcohol consumption without CMP presented significantly lower IGF-1 expression than controls, whereas donors with chronic alcohol consumption with CMP showed a downward trend without achieving significance. CONCLUSIONS: Chronic alcohol consumption significantly reduces IGF-1 myocardial expression. This decrease induced by alcohol is partially compensated in the presence of structural myocardial damage.

19.
Alcohol Alcohol ; 46(5): 534-41, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21733836

RESUMO

AIMS: Although the human heart was classically considered a terminal organ, recent studies have reported a myocyte proliferation response versus some aggressions. Excessive ethanol consumption induces development of cardiomyopathy (CMP) through myocyte apoptosis. We evaluated myocyte proliferation response in the heart of chronic alcoholic donors with telomerase activity (telomerase reverse transcriptase (TERT)) compared with Ki-67 nuclear expression. METHODS: Heart samples were prospectively obtained from organ donors on life support. We included donors with (1) high lifetime alcohol consumption (n = 15), (2) longstanding hypertension (n = 14), (3) other causes of CMP (valve, coronary or idiopathic) (n = 8) and (4) previously healthy donors (n = 6). Groups 2 and 3 were subdivided according to the presence of CMP. Evaluation comprised parameters of ethanol consumption, left ventricular function by chest X-ray and 2D echocardiography, and histology and immunohistochemical studies. Myocyte proliferation was evaluated using an assay for Ki-67 expression and measuring telomerase gene activity by real-time PCR. RESULTS: Forty-three donors were included in the study, 35 having CMP. Nuclear Ki-67 activity was low in healthy controls and significantly increased in the other groups, mainly in those with CMP. Alcoholics with CMP had a non-significantly lower proliferation response than the other CMP groups. No proliferation activity was detected with TERT in any case. CONCLUSION: Heart Ki-67 proliferation activity increases in organ donors with CMP, independently of its origin. Alcoholics presented non-significant lower myocyte proliferation capacity compared with the other groups of CMP. TERT activity was not a useful marker of proliferation in this model. Ki-67 is a better procedure to evaluate proliferation than TERT expression in alcohol-induced heart damage.


Assuntos
Cardiomiopatia Alcoólica/metabolismo , Proliferação de Células/efeitos dos fármacos , Depressores do Sistema Nervoso Central/efeitos adversos , Etanol/efeitos adversos , Antígeno Ki-67/genética , Telomerase/genética , Adulto , Idoso , Alcoólicos , Apoptose , Cardiomiopatia Alcoólica/epidemiologia , Cardiomiopatia Alcoólica/patologia , Feminino , Coração/efeitos dos fármacos , Coração/fisiopatologia , Cardiopatias/metabolismo , Cardiopatias/patologia , Humanos , Hipertensão/patologia , Antígeno Ki-67/biossíntese , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Telomerase/biossíntese , Telomerase/metabolismo , Fatores de Tempo , Doadores de Tecidos
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