RESUMO
Atheromatous plaques occurring in large arteries are common and life-threatening lesions. Multiple factors are involved in the pathogenesis of atheromatous plaques, such as hyperlipidaemia and hypercholesterolaemia, high blood pressure and chronic systemic inflammation. Recent findings have suggested that infection with high-risk human papillomavirus (HPV) may increase the risk of developing atheromatous plaques. However, HPV is considered a tissue-specific virus with a strong tropism towards squamous epithelial cells, and the mechanisms whereby it may promote the development of atheromas remain unclear. Here, we propose a connecting hypothesis to explain the possible causative role of HPV on atheroma development. We hypothesize that HPV infection may promote atheroma formation in infected patients by enhancing systemic inflammation or by directly targeting blood vessels via nucleic acids carried by extracellular vesicles such as exosomes. The pro-inflammatory effects of HPV and the release of extracellular vesicles by HPV-transformed cells are well documented in scientific literature. Possible experimental approaches to test this hypothesis are also discussed, especially experiments employing transgenic mice bearing HPV16 transgenes. If correct, this hypothesis would have major implications for the prevention of cardiovascular diseases, especially due to the preventable nature of HPV infection through vaccination.
Assuntos
Aterosclerose , Infecções por Papillomavirus , Animais , Papillomavirus Humano 16 , Humanos , Camundongos , Camundongos Transgênicos , Infecções por Papillomavirus/complicações , Fatores de RiscoRESUMO
Liver cirrhosis is associated with a wide range of cardiovascular abnormalities including hyperdynamic circulation and cirrhotic cardiomyopathy. The pathogenic mechanisms of these cardiovascular changes are multifactorial and include vascular dysregulations. AIM: The present study tested the hypothesis that the systemic vascular hyporesponsiveness in thioacetamide (TAA)-induced liver injury model is dependent on nitric oxide (NO) and cyclooxygenase (COX) derivatives. MAIN METHODS: Wistar rats were treated with TAA for eight weeks to induce liver injury. KEY FINDINGS: The maximal contractile response in concentration-effect curves to phenylephrine was decreased in aorta from TAA-treated rats, but no differences were found in aorta without endothelium, suggesting an endothelium-dependent mechanism in decreased contractile response. There was no difference in the contractile response with and without L-NAME (N(ω)-nitro-l-arginine methyl ester) in rats with liver injury, showing that the TAA treatment impairs NO synthesis. Pre-incubation of the aorta with indomethacin, a COX-inhibitor, normalized the reduced contractile response to phenylephrine in arteries from TAA group. Also, COX-2 and iNOS (inducible nitric oxide syntase) protein expression was increased in aorta from TAA group compared to control group. Animals submitted to TAA treatment had a reduction in systolic blood pressure. Our findings demonstrated that liver injury induced by TAA caused a decrease in aortic contractile response by a COX-dependent mechanism but not by NO release. Also, it was demonstrated an inflammatory process in the aorta of TAA-treated rats by increased expression of COX-2 and iNOS. SIGNIFICANCE: Therefore, there is an essential contribution of COX-2 activation in extra-hepatic vascular dysfunction and inflammation present in cirrhosis induced by TAA.
Assuntos
Aorta Torácica/patologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Ciclo-Oxigenase 2/metabolismo , Endotélio Vascular/patologia , Tioacetamida/toxicidade , Doenças Vasculares/etiologia , Animais , Aorta Torácica/enzimologia , Pressão Sanguínea , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Endotélio Vascular/enzimologia , Masculino , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Doenças Vasculares/enzimologiaRESUMO
Leptospirosis is globally widespread neglected disease, affecting most mammalian species. Clinical signs can be confused with other diseases which make the diagnosis and treatment difficult. Chemokines and cytokines are known for their role in the inflammatory and immune response to infections. The profile determination of chemokines' expressions in the course of infection may elucidate the defense mechanisms of the host and support the search for effective treatment strategies. We investigated the mechanisms of innate immunity through the comparison of chemokines induced during infection with L. interrogans in mice with different levels of susceptibility. We used lung and spleen tissues samples of mice from C3H/HeJ, C3H/HePas and Balb/c, respectively sensitive, intermediate susceptibility and resistant to the pathogen. The inoculation of L. interrogans in C3H/HeJ mice led a comparatively smaller change in chemokines expression in both spleen and lung tissues. In samples from spleens and lungs of C3H/HePas and Balb/c the higher increases occurred on CXCL9, CXCL16, CXCL5, CCL8 and CCL5 in Balb/c. Given the same genetic background, the differences in the responses of C3H/HePas compared to C3H/HeJ mice strongly suggest the role of chemokines for the survival of parental strain. Therefore, the greatest increase in CXC chemokines appears to be efficient to induce migration of cells to the secondary lymphoid organs and affected tissues, which is important to control infection. Overall, CXC chemokines are important for the activation and attraction of T cell and may influence the course and control of the infection in resistant Balb/c mice.
Assuntos
Quimiocinas/metabolismo , Leptospira/imunologia , Leptospirose/patologia , Pulmão/fisiologia , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Células Cultivadas , Progressão da Doença , Regulação Bacteriana da Expressão Gênica , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Interações Hospedeiro-Patógeno , Imunidade Inata , Mediadores da Inflamação/metabolismo , Leptospirose/imunologia , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
BACKGROUND/OBJECTIVES: The aim of this study was to verify the agreement between body fat percentage (%BF) values evaluated by air displacement plethysmograph (ADP) and body adiposity index (BAI) in adults with Down's syndrome (DS). SUBJECTS/METHODS: Forty-five adults with DS volunteered to participate in this study (19 women; age 28.7±8.5 years and 26 men; age 29.1±8.8 years). The %BF was measured by ADP (%BFADP) and estimated by anthropometric measures [%BF=(hip circumference/height)1.5-18] (%BFBAI). Agreement between methods was evaluated by paired t-test, Pearson's correlation coefficient and Bland-Altman analysis. RESULTS: Although high correlation coefficients were found between %BFADP and %BFBAI for women (r=0.78, P<0.05) and men (r=0.87, P<0.05), significant differences were observed between methods for both sexes (38.9±8.9 vs 42.5±8.5% for women, and 25.8±11.3 vs 32.6±5.4% for men in %BFADP and %BFBAI, respectively). Moreover, Bland-Altman analysis showed that the mean error estimate was +3.6 (95%CI, -7.59 to 14.79) in women and +6.74 (95%CI, -7.25 to 20.72) in men. CONCLUSIONS: The results indicate that BAI seems to be a limited method to evaluate %BF in women and in men with DS.