RESUMO
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: 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
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.