RESUMO
BACKGROUND: Despite intensive training, a few individuals with Type 1 diabetes mellitus (T1DM) fail to reach the desired metabolic targets. AIM: To evaluate the association between disease-related emotional and cognitive aspects and metabolic control in subjects with T1DM. SUBJECTS AND METHODS: Health locus of control (HLOC), sense of coherence (SOC), and self-esteem were assessed in T1DM subjects using validated questionnaires. Sixty-seven consecutive subjects who did not attain the desired HbA1c target (mean HbA1c, 8.3% [67 mmol/mol]) were compared with 30 cases in satisfactory metabolic control (HbA1c levels <7%-53 mmol/mol). RESULTS: In the overall population, SOC was negatively associated with BMI and average HbA1c, as was the association of self-esteem with HbA1c. Subjects attaining the desired metabolic target were characterized by higher SOC scores, higher Internal HLOC and prevalent Internal vs. Powerful-others HLOC. Compared to subjects in good metabolic control, subjects with unsatisfactory control had lower scores of SOC, Internal HLOC and Self-esteem, with no difference in Powerful others, or Chance HLOC. In the same group, SOC in the upper tertile was significantly associated with self-esteem (OR 1.35; 95% CI 1.08-1.69) and PHLOC (OR 1.24; 95% CI 1.03-1.49), after adjustment for age, sex, educational level, and comorbidities. CONCLUSIONS: Patients who fail to reach a satisfactory metabolic control tend to rely on significant others, trusting in the physicians' skills or on the efficiency of the health-care system. Strategies aimed at increasing self-efficacy and SOC, based on personal ability, are eagerly awaited to help patients improve diabetes care.
Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Comportamentos Relacionados com a Saúde , Controle Interno-Externo , Doenças Metabólicas/prevenção & controle , Autoimagem , Senso de Coerência , Adulto , Diabetes Mellitus Tipo 1/psicologia , Feminino , Seguimentos , Humanos , Masculino , Doenças Metabólicas/psicologia , Prognóstico , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND AIMS: Diabetic women have a more adverse plasma lipid profile than men. Sex differences in dietary habits may play a role, but are little investigated. The study evaluates the quality of diet, adherence to the nutritional recommendations of the Diabetes and Nutrition Study Group and their relation with plasma lipid in men and women with diabetes. METHODS AND RESULTS: We studied 2573 people, aged 50-75, enrolled in the TOSCA.IT study (clinicaltrials.gov; NCT00700856). Plasma lipids were measured centrally. Diet was assessed with a semi-quantitative food frequency questionnaire. Women had a more adverse plasma lipid profile than men. Women consumed significantly more legumes, vegetables, fruits, eggs, milk, vegetable oils, and added sugar, whereas men consumed more starchy foods, soft drinks and alcoholic beverages. This stands for a higher proportion (%) of energy intake from saturated fat and added sugar (12.0 ± 2.4 vs 11.5 ± 2.5 and 3.4 ± 3.2 vs 2.3 ± 3.2, P < 0.04), and a higher intake of fiber (11.2 ± 2.8 vs 10.4 ± 2.6 g/1000 Kcal/day) in women. Adherence to the recommendations for saturated fat and fiber consumption was associated with significantly lower LDL-cholesterol regardless of sex. Adherence to the recommendations for added sugars was associated with significantly lower triglycerides and higher HDL-cholesterol in men and women. CONCLUSIONS: Men and women with diabetes show significant differences in adherence to nutritional recommendations, but sex differences in plasma lipid profile are unlikely to be explained by nutritional factors. Adherence to the nutritional recommendations is associated with a better plasma lipid profile regardless of sex, thus reinforcing the importance of substituting saturated for unsaturated fat sources, increasing fiber and reducing added sugar intake.
Assuntos
Comportamento de Escolha , Diabetes Mellitus Tipo 2/dietoterapia , Dieta Saudável , Comportamento Alimentar , Lipídeos/sangue , Cooperação do Paciente , Recomendações Nutricionais , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/psicologia , Feminino , Preferências Alimentares , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
Cardiovascular disease (CVD) is the leading cause of death worldwide and the prevalence of obesity and diabetes are increasing. In obesity, adipose tissue increases the secretion of bioactive mediators (adipokines) that may represent a key mechanism linking obesity to CVD. Adiponectin, extensively studied in metabolic diseases, exerts anti-diabetic, anti-atherogenic and anti-inflammatory activities. Due to these positive actions, the role of adiponectin in cardiovascular protection has been evaluated in recent years. In particular, for its potential therapeutic benefits in humans, adiponectin has become the subject of intense preclinical research. In the cardiovascular context, understanding of the cellular and molecular mechanisms underlying the adiponectin system, throughout its secretion, regulation and signaling, is critical for designing new drugs that target adiponectin system molecules. This review focused on recent advances regarding molecular mechanisms related to protective effects of the adiponectin system on both cardiac and vascular compartments and its potential use as a target for therapeutic intervention of CVD.
Assuntos
Adiponectina/metabolismo , Doenças Cardiovasculares/metabolismo , Adiponectina/genética , Animais , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Inflamação/metabolismo , Miocárdio/metabolismo , Obesidade/metabolismoRESUMO
BACKGROUND AND AIMS: The deregulation of neurohormonal systems, including the natriuretic peptide (NP) and endothelin (ET) systems, may increase the possibility of developing obesity-related risk. The aim of our paper was to evaluate ET system mRNA variation in heart of the Zucker rat model together with the simultaneous evaluation of the NP system transcriptomic profile. In order to analyze the link between the ET-1 system and the inflammatory process, the cardiac expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α was also measured. METHODS AND RESULTS: Zucker rats of 11-13 weeks were subdivided into obese rats (O, n = 20) and controls (CO, n = 20): half of them were studied under fasting conditions (CO(fc)-O(fc)) and the remainder after the induction of acute hyperglycemia (CO(AH)-O(AH)). Cardiac mRNA expression of TNF-α, IL-6, and NP/ET-1 systems was evaluated by Real-Time polymerase chain reaction. No significant difference for pre-proET-1, ET-A, and ET-B mRNA expression was detected between O and CO, whereas significantly lower mRNA levels of the ECE-1 were observed in O (p = 0.02). Regarding NPs, only BNP mRNA expression decreased significantly in O with respect to CO (p = 0.01). A down-regulation of NPR-B and NPR-C and an up-regulation of NPR-A were observed in O. No significant difference for IL-6 and TNF-α mRNA was revealed. Subdividing into fasting and hyperglycemic rats, many of the genes studied maintained their mRNA expression pattern almost unchanged. CONCLUSIONS: The modulation of ET-1/NP systems in obesity could be a useful starting point for future studies aimed at identifying new therapeutic strategies for the treatment of cardiometabolic syndrome.
Assuntos
Endotelinas/metabolismo , Miocárdio/metabolismo , Peptídeos Natriuréticos/metabolismo , RNA Mensageiro/genética , Animais , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Glicemia/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Enzimas Conversoras de Endotelina , Endotelinas/genética , Perfilação da Expressão Gênica , Variação Genética , Interleucina-6/genética , Interleucina-6/metabolismo , Metaloendopeptidases/genética , Metaloendopeptidases/metabolismo , Peptídeos Natriuréticos/genética , Obesidade/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Zucker , Reação em Cadeia da Polimerase em Tempo Real , Receptores do Fator Natriurético Atrial/genética , Receptores do Fator Natriurético Atrial/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Regulação para CimaRESUMO
BACKGROUND AND AIMS: New biomarkers potentially improve clinical management of cardiovascular disease, but there are gaps in understanding their role during childhood. Adiponectin regulates metabolism and exerts anti-inflammatory/anti-atherogenic effects. The aim of the study was to evaluate circulating levels of adiponectin during postnatal growth and its relationship with Brain Natriuretic Peptide (BNP) in healthy children, a marker of cardiac function known to be increased in childhood. METHODS AND RESULTS: Plasma adiponectin and BNP were measured in 131 healthy children divided into: 43 newborns (0-3 days), 29 neonates (4-30 days), 25 infants (1-12 months) and 34 children (1-12 years). A group of 33 healthy adult subjects (25-60 years) was also studied. Plasma adiponectin in the 131 children resulted significantly higher compared to adult subjects (p < 0.0001). The time-course of adiponectin suggests the design of three age-based intervals: the first until 1 month of age (median 29.07 µg/mL, 11.61-47.01 µg/mL 5°-95° percentiles), the second between 1 and 12 months of age (21.66 µg/mL, 8.83-59.81 µg/mL) and the third for age up to 12 years (13.81 µg/mL, 4.10-28.57 µg/mL). Both adiponectin and BNP exhibited the same trend of a progressive decrease during growth, showing a significant relationship (Spearman's rho = 0.403, p < 0.0001). CONCLUSION: Adiponectin plasma levels in a healthy pediatric population vary as a function of age. Three reference intervals for adiponectin in pediatric subjects have been indicated. The relationship between adiponectin and BNP suggests that the age-dependent profile of circulating adiponectin could also be due to BNP.
Assuntos
Adiponectina/sangue , Desenvolvimento Infantil , Regulação para Baixo , Coração/crescimento & desenvolvimento , Peptídeo Natriurético Encefálico/sangue , Adulto , Fatores Etários , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Coração/fisiologia , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
BACKGROUND: Inflammation is a critical process contributing to heart failure (HF). We hypothesized that IL-33/ST2 pathway, a new mechanism regulated during cardiac stress, may be involved in the functional worsening of end-stage HF patients, candidates for left ventricular assist device (LVAD) implantation, and potentially responsible for their outcome. METHODS: IL-33, ST2, and conventional cytokines (IL-6, IL-8, and TNF-α) were determined in cardiac biopsies and plasma of 22 patients submitted to LVAD implantation (pre-LVAD) and compared with (1) control stable chronic HF patients on medical therapy at the moment of heart transplantation without prior circulatory support (HT); (2) patients supported by LVAD at the moment of LVAD weaning (post-LVAD). RESULTS: Cardiac expression of ST2/IL-33 and cytokines was lower in the pre-LVAD than in the HT group. LVAD determined an increase of inflammatory mediators comparable to levels of the HT group. Only ST2 correlated with outcome indices after LVAD implantation. CONCLUSIONS: IL-33/ST2 and traditional cytokines were involved in decline of cardiac function of ESHF patients as well as in hemodynamic recovery induced by LVAD. IL-33/ST2 pathway was also associated to severity of clinical course. Thus, a better understanding of inflammation is the key to achieving more favorable outcome by new specific therapies.
Assuntos
Citocinas/fisiologia , Insuficiência Cardíaca/etiologia , Coração Auxiliar , Mediadores da Inflamação/fisiologia , Interleucinas/fisiologia , Receptores de Superfície Celular/fisiologia , Feminino , Insuficiência Cardíaca/imunologia , Insuficiência Cardíaca/terapia , Transplante de Coração , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina-33 , Masculino , Pessoa de Meia-Idade , Transdução de SinaisRESUMO
Dipyridamole (DP) restores ischemic tissue blood flow stimulating angiogenesis in eNOS-dependent pathways. C-type natriuretic peptide (CNP) is expected to mimic the migration-stimulatory effect of NO via a cGMP-dependent mechanism. Aim of this study was to assess the role of concomitant treatment with DP on CNP levels in blood and myocardial tissue of minipigs with left ventricular dysfunction (LVD) induced by pacing at 200bpm in the right ventricular apex. Minipigs with DP therapy (DP+, n=4) or placebo (DP-, n=4) and controls (C-SHAM, n=4) underwent 2D-EchoDoppler examination and blood collection before and after 4 weeks of pacing, when cardiac tissue was collected. Histological/immunohistochemical analyses were performed. CNP levels were determined by radioimmunoassay; cardiac CNP, BNP, natriuretic receptors expression by Real-Time PCR. After pacing, cardiac parameters resulted less impaired in DP+ compared to DP-. Histological sections presented normal morphology while the arteriolar density resulted: C-SHAM: 9.0±1.2; DP-: 4.9±0.3; DP+: 6.5±0.6number/mm(2); C-SHAM vs DP- and DP+ p=0.004, p=0.04, respectively. CNP mRNA resulted lower in DP- compared to C-SHAM and DP+ as well as NPR-B (p=0.011, DP- vs DP+). Both NPR-A/NPR-C mRNA expressions were significantly (p<0.001) lower both in DP- and DP+ compared to C-SHAM. BNP mRNA was higher in LVD. CNP plasma levels showed a similar trend with respect to gene expression (C-SHAM: 30.5±15; DP-: 18.6±5.5; DP+: 21.2±4.7pg/ml). These data suggest that DP may serve as a preconditioning agent to increase the protective CNP-mediated endocrine response in LVD. This response, mediated by its specific receptor NPR-B, may offer new insights into molecular targets for treatment of LVD.
Assuntos
Dipiridamol/farmacologia , Peptídeo Natriurético Tipo C/metabolismo , Substâncias Protetoras/farmacologia , Disfunção Ventricular Esquerda/metabolismo , Animais , Estimulação Cardíaca Artificial , Dipiridamol/uso terapêutico , Modelos Animais de Doenças , Coração/efeitos dos fármacos , Peptídeo Natriurético Tipo C/genética , Substâncias Protetoras/uso terapêutico , RNA Mensageiro/metabolismo , Suínos , Porco Miniatura , Regulação para Cima , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/genéticaRESUMO
Adult male rats were surgically given a drainage catheter in the main mesenteric lymph duct. After an overnight fast, five groups of rats received intragastrically, in one bolus, butter, corn oil (CO), cod liver oil (CLO), menhaden oil (MO), or ethyl esters of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids (K80). Intestinal lymph was collected in these conscious animals, each hour during the first 6 h and in a single sample for the next 18 h. The absorption peak appeared earlier after MO and CO than after CLO administration. The quantities of triglycerides recovered during the first 6 h were significantly lower after butter (91 mg) and K80 (54 mg) administration than for the other three oils. No difference was observed between the vegetable oil and the marine oils (CO = 173 mg, CLO = 148 mg, MO = 180 mg). The total triglyceride recovered in 24 h was highest after CLO (410 mg) and lowest with K80 (146 mg). An increase in the weight percentage of some characteristic fatty acids of the lipid mixtures was observed: oleic acid for butter, oleic and linoleic acids for CO, EPA and DHA for CLO, MO, and K80. Chylomicrons were the largest with CO, more numerous and smaller with CLO, and the smallest with K80. Results obtained illustrated the relation between gastrointestinal hydrolysis, enterocyte biochemical events, and lymph triglyceride absorption profiles as related to the composition and distribution of triglyceride fatty acids.
Assuntos
Manteiga , Óleo de Fígado de Bacalhau , Óleo de Milho , Gorduras na Dieta/farmacocinética , Ácidos Docosa-Hexaenoicos/farmacocinética , Ácido Eicosapentaenoico/farmacocinética , Óleos de Peixe , Absorção Intestinal , Linfa/fisiologia , Triglicerídeos/metabolismo , Animais , Ácido Eicosapentaenoico/análogos & derivados , Masculino , Ratos , Ratos Wistar , Fatores de TempoRESUMO
The high prevalence of obesity in children may increase the magnitude of lifetime risk of cardiovascular disease (CD). At present, explicit data for recommending biomarkers as routine pre-clinical markers of CD in children are lacking. C-type natriuretic peptide (CNP) is assuming increasing importance in CD; in adults with heart failure, its plasma levels are related to clinical and functional disease severity. We have previously reported five different reference intervals for blood CNP as a function of age in healthy children; however, data on plasma CNP levels in obese children are still lacking. Aim of this study was to assess CNP levels in obese adolescents and verify whether they differ from healthy subjects. Plasma CNP was measured in 29 obese adolescents (age: 11.8 ± 0.4 years; BMI: 29.8 ± 0.82) by radioimmunoassay and compared with the reference values of healthy subjects. BNP was also measured. Both plasma CNP and BNP levels were significantly lower in the obese adolescents compared to the appropriate reference values (CNP: 3.4 ± 0.2 vs 13.6 ± 2.3 pg/ml, p<0.0001; BNP: 18.8 ± 2.6 vs 36.9 ± 5.5 pg/ml, p=0.003). There was no significant difference between CNP values in males and females. As reported in adults, we observed lower plasma CNP and BNP levels in obese children, suggesting a defective natriuretic peptide system in these patients. An altered regulation of production, clearance and function of natriuretic peptides, already operating in obese adolescents, may possibly contribute to the future development of CD. Thus, the availability of drugs promoting the action of natriuretic peptides may represent an attractive therapeutic option to prevent CD.
Assuntos
Peptídeo Natriurético Encefálico/sangue , Peptídeo Natriurético Tipo C/sangue , Obesidade/sangue , Adolescente , Adulto , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Criança , Feminino , Humanos , Masculino , Obesidade/complicações , Radioimunoensaio , Valores de ReferênciaRESUMO
The aim of this study was to evaluate the transcriptomic profiling of C-type natriuretic peptide (CNP) and of its specific receptor, NPR-B in human leukocytes of heart failure (HF) patients as a function of clinical severity, assessing the possible changes with respect to healthy subjects (C). mRNA expression was evaluated by Real-Time PCR and total RNA was extracted from leukocytes of C (n=8) and of HF patients (NYHA I-II, n=7; NYHA III-IV, n=13) with PAXgene Blood RNA Kit. Significantly higher levels of CNP mRNA expression were found in HF patients as a function of clinical severity (C=0.23±0.058, NYHA I-II=0.47±0.18, NYHA III-IV=2.58±0.71, p=0.005 C vs NYHA III-IV, p=0.017 NYHA I-II vs NYHA III-IV) and NPR-B transcript levels resulted down-regulated in HF patients with higher NYHA class (C=2.2±0.61, NYHA I-II=2.76±0.46, NYHA III-IV=0.29±0.13, p=0.001 C vs NYHA III-IV, p<0.0001 NYHA I-II vs NYHA III-IV). A significant negative correlation between CNP and NPR-B mRNA expression (r=0.5, p=0.03) was also observed. These results suggest a co-regulation of NPR-B and CNP expression supporting the relevance of this receptor in human disease characterized by a marked inflammatory/immune component and suggesting the possibility of manipulating inflammation via pharmacological agents selective for this receptor.
Assuntos
Insuficiência Cardíaca/genética , Peptídeo Natriurético Tipo C/genética , RNA Mensageiro/genética , Receptores do Fator Natriurético Atrial/genética , Adulto , Doença Crônica , Feminino , Perfilação da Expressão Gênica , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Tipo C/metabolismo , RNA Mensageiro/metabolismo , Receptores do Fator Natriurético Atrial/metabolismo , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Vasculogenesis is a hallmark of myocardial restoration. Post-ischemic late remodeling is associated with pathology and function worsening. At the same time, neo-vasculogenesis helps function improving and requires the release of vascular endothelial growth factor type A (VEGF-A). The vasculogenic role of C-type natriuretic peptide (CNP), a cardiac paracrine hormone, is unknown in infarcted hearts with preserved left ventricular (LV) ejection fraction (EF). We explored whether myocardial VEGF-dependent vasculogenesis is affected by CNP. METHODS AND RESULTS: To this end, infarcted swine hearts were investigated by magnetic resonance imaging (MRI), histological and molecular assays. At the fourth week, MRI showed that transmural myocardial infarction (MI) affected approximately 13% of the LV wall mass without impairing global function (LVEF>50%, n=9). Increased fibrosis, metalloproteases and capillary density were localized to the infarct border zone (BZ), and were associated with increased expression of CNP (p=0.03 vs. remote zone (RZ)), VEGF-A (p<0.001 vs. RZ), BNP, a marker of myocardial dysfunction (p<0.01 vs. RZ) and the endothelial marker, factor VIII-related antigen (p<0.01 vs. RZ). In vitro, CNP 1000 nM promoted VEGF-dependent vasculogenesis without affecting the cell growth and survival, although CNP 100 nM or a high concentration of VEGF-A halted vascular growth. CONCLUSIONS: CNP expression is locally increased in infarct remodeled myocardium in the presence of dense capillary network. The vasculogenic response requires the co-exposure to high concentration of CNP and VEGF-A. Our data will be helpful to develop combined myocardial delivery of CNP and VEGF-A genes in order to reverse the remodeling process.
Assuntos
Infarto do Miocárdio/fisiopatologia , Peptídeo Natriurético Tipo C/fisiologia , Neovascularização Fisiológica/fisiologia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Função Ventricular Esquerda , Remodelação Ventricular , Animais , Masculino , SuínosRESUMO
This study aimed to evaluate left ventricular assist device (LVAD) effects on natriuretic peptide (NP) prohormone plasma levels in end-stage heart failure (HF) patients, especially NT-proCNP, in order to better characterize the NP system during hemodynamic recovery by LVAD. HF patients (n=17, NYHA III-IV) undergoing LVAD were studied: 6 died of multi-organ failure syndrome (NS) and 11 survived (S). Total sequential organ failure assessment (t-SOFA) score and blood samples were obtained at admission (T1) and at 24, 72h and 1, 2, 4 weeks (T2-T6) after LVAD. In S, NT-proANP and NT-proCNP significantly increased at 24h after implantation, reaching a reduction to basal levels at 4 weeks following LVAD [NT-proANP: T1 vs. T2 p=0.017, NT-proCNP: T1 vs. T2 p=0.028, T1 vs. T3 p=0.043]. Elevated NT-proBNP plasma levels were observed at all times. In NS, NP plasma levels sustained higher with respect to S. No statistical variation was observed for NT-proCNP and NT-proANP in S and NS while NT-proBNP reached significant differences at T4 in NS. Considering S+NS, only NT-proCNP strongly correlated with t-SOFA score at T1 (rho=0.554, p=0.04) while subdividing patients NT-proCNP positively correlated in NS with t-SOFA score (rho=0.988, p=0.002) only at T4. In NS a correlation between NT-proCNP and NT-proBNP at T1 was observed (rho=-0.900, p=0.037). Both IL-6 and TNF-alpha sustained higher in NS patients than in S; in particular, statistical significance was observed for IL-6. The study of new peptides, such as NT-proCNP, would provide additional information for identifying patients who are more likely to recover.
Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Coração Auxiliar , Peptídeo Natriurético Tipo C/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangueRESUMO
C-type natriuretic peptide (CNP) is assuming increasing importance in cardiovascular disease, and in adults its plasma levels are related to clinical and functional disease severity. Data are scarce regarding the reference values for CNP in infancy. Aim of this study was to assess the reference intervals for CNP in human healthy newborns and infants. Plasma CNP was measured in 121 healthy children divided into: 41 newborns (age 0-3 days), 24 newborns (4-30 days), 22 infants (1-12 months) and 32 children (1-12 years). A group of 32 healthy adult subjects (age 64 ± 1 years) was also studied. CNP was measured by a specific radioimmunoassay. Between- and within-assay variability resulted ≤ 30 and 20%, respectively and analytical sensitivity 0.77 ± 0.05 pg/tube. Plasma CNP resulted significantly higher in children than in adult subjects (13.6 ± 1.2 pg/ml vs. 7.4 ± 1.0 pg/ml, p=0.030). When the results were analyzed as a function of the age the reference intervals for plasma CNP resulted: 11.6 ± 2.1 pg/ml for newborns (0-3 days), 16.4 ± 3.7 pg/ml for newborns (4-30 days), 15.4 ± 2.7 pg/ml for infants (1-12 months), 13.6 ± 2.3 pg/ml for children (1-12 years) [p=0.01 newborns (4-30 days) vs. adults; p=0.03 infants (1-12 months) vs. adults]. CNP showed the highest concentrations after 12h of life with a peak between 4 and 5 days of life and with a progressive decline afterwards. According to these data at least five different reference intervals for CNP determinations should be used. These observations may be helpful for future clinical application of CNP in human children.
Assuntos
Peptídeo Natriurético Tipo C/sangue , Idoso , Índice de Apgar , Peso Corporal , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
C-type natriuretic peptide (CNP), a member of the family of natriuretic peptides, is synthesized and secreted from monocytes and macrophages that resulted to be a source of CNP at inflammatory sites. This suggests that special attention should be focused on the possible role of CNP in the immune system, in addition to its effects on the cardiovascular system. The aim of this study was to evaluate the possibility of measuring the mRNA expression of CNP and NPR-B, its specific receptor, in human whole blood samples of healthy (N; n=7) and heart failure (HF; n=7) subjects by Real-Time PCR (RT-PCR). Total RNA was extracted from leukocytes with QIAamp RNA Blood Kit and/or with PAXgene Blood RNA Kit. RT-PCR was performed and optimized for each primer. The experimental results were normalized with the three most stably expressed genes. CNP and NPR-B expression trend was similar in both fresh and frozen human whole blood. Significant higher levels of CNP and NPR-B mRNA expression were found in HF patients with respect to controls (CNP: N=1.23±0.33 vs. HF=6.54±2.09 p=0.027; NPR-B: N=0.85±0.23 vs. HF=5.31±1.98 p=0.04). A significant correlation between CNP and NPR-B (r=0.86, p<0.0001) was observed. Further studies are needed to clarify the pathophysiological properties of this peptide but the possibility to measure CNP and NPR-B mRNA expression in human leukocytes with a fast and easy procedure is a useful starting point for future investigation devoted to better understand the biomolecular processes associated to different diseases.
Assuntos
Perfilação da Expressão Gênica , Saúde , Insuficiência Cardíaca/genética , Leucócitos/metabolismo , Peptídeo Natriurético Tipo C/genética , Receptores do Fator Natriurético Atrial/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
C-type natriuretic peptide (CNP) was recently found in myocardium at the mRNA and protein levels, but it is not known whether cardiomyocytes are able to produce CNP. The aim of this study was to determine the expression of CNP and its specific receptor NPR-B in cardiac cells, both in vitro and ex vivo. CNP, brain natriuretic peptide (BNP) and natriuretic peptide receptor (NPR)-B mRNA expression were examined by RT-PCR in the H9c2 rat cardiac myoblast cell line, in neonatal rat primary cardiomyocytes and in human umbilical vein endothelial cells (HUVECs) as control. CNP protein expression was probed in cardiac tissue sections obtained from adult male minipigs by immunohistochemistry, and in H9c2 cells both by immunocytochemistry and by specific radioimmunoassay. The results showed that cardiac cells as well as endothelial cells were able to produce CNP. Unlike cardiomyocytes, as expected, in endothelial cells expression of BNP was not detected. NPR-B mRNA expression was found in both cell types. Production of CNP in the heart muscle cells at protein level was confirmed by radioimmunological determination (H9c2: CNP=0.86 ± 0.083 pg/mg) and by immunocytochemistry studies. By immunostaining of tissue sections, CNP was detected in both endothelium and cardiomyocytes. Expression of CNP in cardiac cells at gene and protein levels suggests that the heart is actively involved in the production of CNP.
Assuntos
Miócitos Cardíacos/metabolismo , Peptídeo Natriurético Tipo C/genética , Receptores do Fator Natriurético Atrial/genética , Animais , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Peptídeo Natriurético Tipo C/metabolismo , RNA Mensageiro/metabolismo , Ratos , Receptores do Fator Natriurético Atrial/metabolismoRESUMO
Pharmacological treatments able to activate natriuretic receptors (NPRs) and inhibit cardiac remodelling in heart failure (HF) patients, are currently under investigation. To better understand the therapeutic potential of the NPRs activation is necessary to dispose of experimental models devoid of confounding effects. The pig constitutes an animal model largely used but its genome is not completely sequenced. Aims of this study were to sequence NPR-A and NPR-C in Susscrofa and to evaluate ANP, BNP and NPRs mRNA expression in cardiac tissue of normal and HF minipigs in order to have a starting point for future studies devoted to check new potential drugs. Cardiac tissue was collected from adult male minipigs without (n=4) and with HF (n=5). Pig NPR-A (179bp) and NPR-C (203bp) mRNA were partially sequenced (GenBank n.: FJ518622, FJ518621). Compared to control, ANP and BNP gene expression resulted higher in all the cardiac chambers of HF heart. This increase is associated to a down-regulation of NPR-A and an up-regulation of NPR-C in HF. These sequences will provide a new tool to investigate the role of natriuretic peptides and of their receptors under physiological and pathological conditions and their response to therapeutic interventions.
Assuntos
Modelos Animais de Doenças , Insuficiência Cardíaca/metabolismo , Miocárdio/metabolismo , Receptores do Fator Natriurético Atrial/metabolismo , Animais , Sequência de Bases , Estudos de Casos e Controles , Primers do DNA , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência do Ácido Nucleico , Suínos , Porco MiniaturaAssuntos
Gorduras na Dieta/metabolismo , Absorção Intestinal , Lipoproteínas VLDL/metabolismo , Linfa , Óleos/metabolismo , Animais , Arachis , Brassica , Quilomícrons/metabolismo , Ácidos Erúcicos/metabolismo , Ácidos Graxos Insaturados/metabolismo , Mucosa Intestinal/metabolismo , Linfa/análise , Masculino , Microscopia Eletrônica , Ácidos Oleicos/metabolismo , Ratos , Zea maysAssuntos
Aeromonas/ultraestrutura , Crustáceos/microbiologia , Vibrio cholerae/ultraestrutura , Aeromonas/enzimologia , Aeromonas/isolamento & purificação , Animais , Quitinases/análise , Água Doce , Itália , Microscopia Eletrônica de Varredura , Estações do Ano , Vibrio cholerae/enzimologia , Vibrio cholerae/isolamento & purificaçãoRESUMO
Rats were fed on a 20% fat diet; 30 min. or 2 hrs later intestinal jejunal cells were fixed in situ; samples were taken and processed for subsequent study by electron microscopy. Chylomicron secretion was followed from the enterocyte to the lymphatic capillary lumen. Chylomicrons entered the lamina propria through breaks in the basal membrane at intercellular space level. Their penetration into the lymphatic capillary lumen occurred through the open junctions of the endothelial cells normally kept closed by desmosomal formations.