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1.
Diabetes ; 70(1): 196-203, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33055188

RESUMO

Activation of the mineralocorticoid receptor (MR) may promote dysfunctional adipose tissue in patients with type 2 diabetes, where increased pericellular fibrosis has emerged as a major contributor. The knowledge of the association among the MR, fibrosis, and the effects of an MR antagonist (MRA) in human adipocytes remains very limited. The present substudy, including 30 participants, was prespecified as part of the Mineralocorticoid Receptor Antagonist in Type 2 Diabetes (MIRAD) trial, which randomized patients to either high-dose eplerenone or placebo for 26 weeks. In adipose tissue biopsies, changes in fibrosis were evaluated by immunohistological examination and by the expression of mRNA and protein markers of fibrosis. Treatment with an MRA reduced pericellular fibrosis, synthesis of the major subunits of collagen types I and VI, and the profibrotic factor α-smooth muscle actin compared with placebo in subcutaneous adipose tissue. Furthermore, we found decreased expression of the MR and downstream molecules neutrophil gelatinase-associated lipocalin, galectin-3, and lipocalin-like prostaglandin D2 synthase with an MRA. In conclusion, we present original data demonstrating reduced fibrosis in adipose tissue with inhibition of the MR, which could be a potential therapeutic approach to prevent the extracellular matrix remodeling of adipose tissue in type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/patologia , Eplerenona/uso terapêutico , Fibrose/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Gordura Subcutânea/efeitos dos fármacos , Actinas/metabolismo , Idoso , Colágeno Tipo I/metabolismo , Colágeno Tipo VI/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Eplerenona/farmacologia , Feminino , Fibrose/metabolismo , Fibrose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Gordura Subcutânea/metabolismo , Gordura Subcutânea/patologia
2.
ESC Heart Fail ; 6(5): 983-991, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31429530

RESUMO

AIMS: Cardiac cachexia is a wasting syndrome characterized by chronic inflammation and high mortality. Fibroblast growth factor 21 (FGF-21) and monocyte chemoattractant protein 1 (MCP-1) are associated with cardiovascular disease and systemic inflammation. We investigated FGF-21 and MCP-1 in relations to cardiac function, inflammation, and wasting in patients with heart failure with reduced ejection fraction (HFrEF) and cardiac cachexia. METHODS AND RESULTS: Plasma FGF-21 and MCP-1 were measured in a cross-sectional study among the three study groups: 19 patients with HFrEF with cardiac cachexia, 19 patients with HFrEF without cachexia, and 19 patients with ischaemic heart disease and preserved ejection fraction. Patients with HFrEF and cardiac cachexia displayed higher FGF-21 levels median (inter quantile range) 381 (232-577) pg/mL than patients with HFrEF without cachexia 224 (179-309) pg/mL and ischaemic heart disease patients 221 (156-308) pg/mL (P = 0.0496). No difference in MCP-1 levels were found among the groups (P = 0.345). In a multivariable regression analysis, FGF-21 (logarithm 2) was independently associated with interleukin 6 (logarithm 2) (P = 0.015) and lower muscle mass (P = 0.043), while no relation with N-terminal pro-hormone brain natriuretic peptide was observed. CONCLUSIONS: Fibroblast growth factor 21 (FGF-21) levels were elevated in patients with HFrEF and cardiac cachexia, which could be mediated by increased inflammation and muscle wasting rather than impaired cardiac function.


Assuntos
Biomarcadores/sangue , Quimiocina CCL2/metabolismo , Fatores de Crescimento de Fibroblastos/sangue , Inflamação/metabolismo , Síndrome de Emaciação/metabolismo , Idoso , Idoso de 80 Anos ou mais , Caquexia/complicações , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Estudos de Casos e Controles , Doença Crônica , Estudos Transversais , Dinamarca/epidemiologia , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Interleucina-6/sangue , Masculino , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Isquemia Miocárdica/sangue , Isquemia Miocárdica/fisiopatologia , Peptídeo Natriurético Encefálico/sangue , Volume Sistólico/fisiologia , Síndrome de Emaciação/mortalidade , Síndrome de Emaciação/patologia
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