RESUMO
PURPOSE: Bariatric surgery (BS) promotes carotid intima-media thickness (C-IMT) regression as early as 6 months post-surgery. To verify whether C-IMT regression occurs even earlier, we aimed at the effect of Roux-en-Y gastric bypass (RYGBP) and biliopancreatic diversion (BPD) on C-IMT 1-2 months and 12 months post-surgery. SUBJECTS/METHODS: Prospective trial. BS was performed on 109 patients either with (RYGBP = 42; BDP = 40) or without type 2 diabetes (RYGBP = 27). Healthy volunteers served as control group. FOLLOW-UP: baseline, 1-2 months, 12 months post-surgery. ENDPOINTS: changes (∆) in C-IMT, weight, body mass index, fat mass, waist and neck circumferences, blood pressure, HbA1c, glucose, insulin, insulin sensitivity [HOMA-IR; OGIS, from meal tolerance test], lipids, C-reactive protein, leptin, adiponectin, MCP-1. RESULTS: All surgery subgroups had similar levels of ∆-C-IMT. C-IMT in the pooled surgery group reduced from [mean (95% confidence interval)] 0.81 (0.77-0.84) mm to 0.66 (0.63-0.69) mm, p < 0.001 [-17.1 (-20.4 to -13.8)%] at 1-2 months, and to 0.63 (0.59-0.66) mm, p < 0.001 [-21.8 (-25.3 to -18.4)%] at 12 months post-surgery. ∆-C-IMT 1-2 months and 12 months post-surgery correlated to baseline C-IMT, and with ∆-leptin at 1-2 months, but not at 12 months post-surgery. In linear regression analysis, ∆-leptin and baseline C-IMT were predictors of ∆-C-IMT 1-2 months post-surgery. CONCLUSIONS: A remarkable C-IMT regression occurred as early as 1-2 months after BS in obese patients either with or without type 2 diabetes, which was associated to the early reduction in leptin, (at least partially) independent of weight loss. Whether this is a causative or correlative association needs further investigation.
Assuntos
Cirurgia Bariátrica , Espessura Intima-Media Carotídea , Diabetes Mellitus Tipo 2/cirurgia , Leptina/sangue , Obesidade/cirurgia , Adulto , Cirurgia Bariátrica/reabilitação , Índice de Massa Corporal , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/fisiopatologia , Obesidade Mórbida/sangue , Obesidade Mórbida/complicações , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/cirurgia , Fatores de Tempo , Túnica Íntima/diagnóstico por imagem , Túnica Íntima/patologia , Redução de Peso/fisiologia , Adulto JovemRESUMO
AIMS/HYPOTHESIS: Bariatric surgery is currently employed as an effective approach to treat class III obesity and class II obesity with co-morbidities. Unfortunately, the general anthropometric and metabolic outcomes of the surgery are not homogeneous, and defining the eligibility criteria that allow for a more precise prediction of the outcomes of this invasive procedure will refine the selection of patients. Here we tested the hypothesis that the Gly482Ser polymorphism of the ppargc1a gene would predict different outcomes following bariatric surgery. METHODS: Fifty-five patients (26 Gly/Gly and 29 Gly/Ser+Ser/Ser) selected for the Roux-en-Y gastric bypass according to the National Institutes of Health Consensus Statement criteria were followed up for 1 year, monitoring their anthropometric, metabolic and inflammatory parameters. RESULTS: Patients with the Gly482Ser polymorphism had significantly improved reductions in the waist/hip ratio, fasting blood glucose, C-reactive protein, blood leukocyte count, serum interleukin-6 and intima-media thickness of the carotid artery, as compared with Gly/Gly patients. CONCLUSIONS/INTERPRETATION: Thus, the Gly482Ser polymorphism may predict a more favorable metabolic and inflammatory outcome for obese patients submitted to bariatric surgery, leading to a reduced atherosclerotic risk.
Assuntos
Doença da Artéria Coronariana/prevenção & controle , Derivação Gástrica , Obesidade Mórbida/genética , Obesidade Mórbida/cirurgia , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Brasil/epidemiologia , Proteína C-Reativa/genética , Espessura Intima-Media Carotídea , Comorbidade , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/patologia , Feminino , Derivação Gástrica/métodos , Glicina , Humanos , Interleucina-6/genética , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/epidemiologia , Reação em Cadeia da Polimerase , Serina , Resultado do Tratamento , Redução de Peso , Adulto JovemRESUMO
The heart responds to sustained overload by hypertrophic growth in which the myocytes distinctly thicken or elongate on increases in systolic or diastolic stress. Though potentially adaptive, hypertrophy itself may predispose to cardiac dysfunction in pathological settings. The mechanisms underlying the diverse morphology and outcomes of hypertrophy are uncertain. Here we used a focal adhesion kinase (FAK) cardiac-specific transgenic mice model (FAK-Tg) to explore the function of this non-receptor tyrosine kinase on the regulation of myocyte growth. FAK-Tg mice displayed a phenocopy of concentric cardiac hypertrophy, reflecting the relative thickening of the individual myocytes. Moreover, FAK-Tg mice showed structural, functional and molecular features of a compensated hypertrophic growth, and preserved responses to chronic pressure overload. Mechanistically, FAK overexpression resulted in enhanced myocardial FAK activity, which was proven by treatment with a selective FAK inhibitor to be required for the cardiac hypertrophy in this model. Our results indicate that upregulation of FAK does not affect the activity of Src/ERK1/2 pathway, but stimulated signaling by a cascade that encompasses PI3K, AKT, mTOR, S6K and rpS6. Moreover, inhibition of the mTOR complex by rapamycin extinguished the cardiac hypertrophy of the transgenic FAK mice. These findings uncover a unique role for FAK in regulating the signaling mechanisms that governs the selective myocyte growth in width, likely controlling the activity of PI3K/AKT/mTOR pathway, and suggest that FAK activation could be important for the adaptive response to increases in cardiac afterload. This article is part of a Special Issue entitled "Local Signaling in Myocytes".
Assuntos
Cardiomegalia/enzimologia , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Animais , Cardiomegalia/genética , Cardiomegalia/patologia , Feminino , Proteína-Tirosina Quinases de Adesão Focal/genética , Expressão Gênica , Ordem dos Genes , Vetores Genéticos , Masculino , Camundongos , Camundongos Transgênicos , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidoresRESUMO
We investigated the possible role of Mannose binding lectin 2 (MBL2) functional polymorphisms in the prevalence of hypertension and hypertensive end-organ damage in 300 hypertensive patients and 313 normotensive individuals from Southern Brazil. Hypertensive subjects with MBL2 AO/OO genotypes presented lower C-reactive protein levels than AA individuals and consequently lower inflammatory status.
Assuntos
Predisposição Genética para Doença , Hipertensão/complicações , Hipertensão/genética , Inflamação/complicações , Inflamação/genética , Lectina de Ligação a Manose/genética , Polimorfismo de Nucleotídeo Único/genética , Brasil , Proteína C-Reativa/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
STUDY DESIGN: This is cross-sectional study. OBJECTIVES: The aim of this study is to investigate the cardiac structure and function of subjects with spinal cord injury (SCI) and the impact of metabolic, hemodynamic and inflammatory factors on these parameters. SETTING: São Paulo, Brazil. METHODS: Sixty-five nondiabetic, nonhypertensive, sedentary, nonsmoker men (34 with SCI and 31 healthy subjects) were evaluated by medical history, anthropometry, laboratory tests, analysis of hemodynamic and inflammatory parameters and echocardiography. RESULTS: Subjects with SCI had lower systolic blood pressure and higher levels of C-reactive protein and tumor necrosis factor receptors than the healthy ones. Echocardiography data showed that the SCI group presented similar left ventricular (LV) structural and systolic parameters, but lower initial diastolic velocity (Em) (9.2 ± 0.5 vs 12.3 ± 0.5 cm s(-1); P<0.001) and higher peak early inflow velocity (E)/Em ratio (7.7 ± 0.5 vs 6.1 ± 0.3; P = 0.009) compared with the able-bodied group, even after adjustment for systolic blood pressure and C-reactive protein levels. Furthermore, injured subjects with E/Em >8 had lower peak spectral longitudinal contraction (Sm) (9.0 ± 0.7 vs 11.6 ± 0.4 cm s(-1); P<0.001) and cardiac output (4.2 ± 0.2 vs 5.0 ± 0.2 l min(-1); P = 0.029), as well as higher relative wall thickness (0.38 ± 0.01 vs 0.35 ± 0.01; P = 0.005), than individuals with SCI with E/Em<8, but similar age, body mass index, blood pressure, injury level, metabolic parameters and inflammatory marker levels. CONCLUSION: Subjects with SCI presented impaired LV diastolic function in comparison with able-bodied ones. Moreover, worse LV diastolic function was associated with a pattern of LV concentric remodeling and subclinical decreases in systolic function among injured subjects. Overall, these findings might contribute to explain the increased cardiovascular risk reported for individuals with SCI.
Assuntos
Insuficiência Cardíaca Diastólica/epidemiologia , Insuficiência Cardíaca Diastólica/fisiopatologia , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/fisiopatologia , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Brasil/epidemiologia , Comorbidade/tendências , Estudos Transversais , Insuficiência Cardíaca Diastólica/diagnóstico , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/inervação , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Ultrassonografia , Disfunção Ventricular Esquerda/diagnósticoRESUMO
STUDY DESIGN: Cross-sectional. OBJECTIVES: Individuals with spinal cord injury (SCI) exhibit increased carotid intima-media thickness (IMT) and are reported to be exposed to higher circulating levels of inflammatory mediators. This study evaluated the relationship between inflammatory markers and carotid surrogates of cardiovascular risk in subjects with SCI. SETTING: São Paulo, Brazil. METHODS: A total of 65 nondiabetic, nonhypertensive, sedentary, nonsmoker men (34 with SCI; 31 healthy subjects) were evaluated by medical history, anthropometry, routine laboratory tests, analysis of hemodynamic, inflammatory parameters and ultrasound examination of carotid arteries. RESULTS: Subjects with SCI (18 tetraplegic and 16 paraplegic) had lower systolic blood pressure (P = 0.009), higher serum C-reactive protein (P = 0.001), tumor necrosis factor (TNF) receptor-II (P = 0.02) and TNF receptor-I (P = 0.04) levels and increased in vitro production of interleukin-6 by mononuclear cells (P = 0.04), compared to able-bodied individuals. No differences in serum interleukin-6, e-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and transforming growth factor-ß levels, or in vitro release of interleukin-10, interleukin-17 and interferon-γ by mononuclear cells, were detected between the studied groups. Common carotid IMT, but not internal carotid resistive index, was significantly higher in subjects with SCI (P<0.0001 adjusted for C-reactive protein and TNF receptor-II levels). In addition, tetraplegic subjects exhibited increased IMT (P = 0.002 adjusted for systolic blood pressure and body mass index), but similar levels of inflammatory mediators compared to paraplegic ones. CONCLUSIONS: Individuals with SCI exhibit a clustering of vascular and inflammatory surrogates of increased cardiovascular risk. Nevertheless, subclinical carotid atherosclerosis is related to injury level but not to increased inflammatory status in these subjects.