ABSTRACT
BACKGROUND: Chagas disease is considered important and presents intense inflammatory and fibrotic processes induced by the perpetuation of the parasite in the affected tissues and organs. Therefore, it is necessary to inquire about the host defense and attack mechanisms to have a more detailed knowledge about Chagas disease. Micro-RNAs are found in blood, tissues and extracellular vesicles. These small regulators of gene expression are involved in physiological and pathological processes in both mammals and parasites. Several microRNAs have deregulated expression in chagasic heart disease, although little is known about their extracellular expression. Our main objective was to evaluate the involvement of miR-21, miR-146a and miR-155 in several samples from mice infected with the TcI Ninoa strain from the acute and indeterminate phases. We also explored a potential functional association of the selected microRNAs using STRING software. This software identified 23 pathways associated with Trypanosoma cruzi infection. In addition, eleven genes were identified through bioinformatics analysis, and we found that SMAD family member 5 was downregulated in both phases. This gene serves as a mediator in the TGF-ß signaling pathway. Thus, forty female mice of the CD1 strain were distributed into 4 groups and the expression levels of miR-21, miR-146a and miR-155 were measured in samples of heart tissue, total plasma and plasma extracellular vesicles by quantitative real-time polymerase chain reaction. RESULTS: Overexpression of miR-21, miR-146a and miR-155 was observed in heart and plasma in both phases. Moreover, in extracellular vesicles miR-21 and miR-146a were also overexpressed in the acute phase, whereas in the indeterminate chronic phase we found only miR-146a up-regulated. CONCLUSIONS: The expression of inflammatory microRNAs miR-21, miR-146a and miR-155 were up-regulated in each of the samples from acutely and chronically infected mice. The relevant finding was that miR-146a was up-regulated in each sample in both phases; therefore, this miRNA could be a possible candidate biomarker in Chagas disease.
Subject(s)
Animals , Female , Mice , Chagas Disease/genetics , MicroRNAs/genetics , Fibrosis , Biomarkers , Computational BiologyABSTRACT
La omentina es una nueva adipocina a la que se le ha atribuido la capacidad de regular actividades metabólicas (sensibilidad a la insulina) y antiinflamatorias, ofreciendo protección cardiovascular en la obesidad y diabetes mellitus tipo 2. Por lo anterior, es importante conocer los mecanismos a través de los cuales confiere protección cardiovascular, con el objetivo de considerar la omentina como blanco o agente terapéutico en este escenario.
The omentin is an adipokine, which role is due to the capacity of regulate metabolic (insulin sensitivity) and anti-inflammatory activities, thus conferring vascular protection during obesity and diabetes mellitus type 2. By this, it is important to know the mechanisms by which omentin confers cardiovascular protection, with the purpose of establish omentin a possible therapeutic target or molecule on this scenario.
Subject(s)
Humans , Cardiovascular Diseases/etiology , Cytokines/physiology , Inflammation/etiology , Lectins/physiology , Insulin Resistance/physiology , Endothelium, Vascular/physiopathology , Energy Metabolism , GPI-Linked Proteins/physiology , Obesity/etiologyABSTRACT
En esta segunda parte de nuestra revisión se propone a la solución polarizante como una alternativa más, además de otras ya existentes, para el mantenimiento de las células cardíacas durante un infarto, apoyado en el cambio metabólico cardíaco durante la hipoxia.
Based on the cardiac metabolic changes during hypoxia, in this second part of our review we propose, the polarizing solution as an alternative for the maintenance of the cardiac cells during an infarction, in conjunction with other alternative therapies.
Subject(s)
Animals , Humans , Rats , Hypoxia/metabolism , Glucose/therapeutic use , Insulin/therapeutic use , Monosaccharide Transport Proteins/therapeutic use , Myocardial Ischemia/metabolism , Myocardium/metabolism , Potassium/therapeutic use , Clinical Trials as Topic , Myocardial Ischemia/drug therapyABSTRACT
The protective role of estrogens against peripheral vascular and coronary disease in women is well documented; however, it is not present in diabetic women. Estrogens reduce tension development through non-genomic mechanisms that include changes in calcium concentrations in endothelial and smooth muscle cells, and regulation of nitric oxide synthase (NOS) in endothelial cells. Insulin increases endothelin-1 (ET-1) release from endothelial cells modulating smooth muscle calcium levels and elevating force generated by femoral and coronary arteries. This paper examines whether 17/β-estradiol (E2β) modulates changes in femoral and coronary artery contractility induced by insulin. Femoral and coronary arteries were obtained from male Wistar rats, placed in isolated tissue baths for in vitro studies, perfused with different solutions, and the contractile response to KCl 40 mmol/L was measured. Insulin increased arterial contraction induced by KCl. This increase was not present when the endothelium was removed. In the presence of E2β, we observed a dose dependent reduction in the tension developed and this effect disappeared when the endothelium was removed. The insulin-induced contraction was significantly reduced in presence of E2β. These data indicate that the effect of insulin on femoral and coronary vascular contractility is modulated by E2β.
Los estrógenos protegen a la mujer contra enfermedades vasculares periféricas y centrales; sin embargo, su papel se pierde con la diabetes. Los estrógenos reducen la tensión en las arterias mediante cambios en el calcio intracelular en células endoteliales y musculares lisas y la regulación de la óxido nítrico sintasa en células endoteliales. La insulina incrementa la liberación de endotelina-1 (ET-1) en células endoteliales aumentando la fuerza generada por las arterias. En este estudio se examina si el 17/β-estradiol (E2β) modula los cambios en la contractilidad inducidos por insulina en las arterias femorales y coronarias. Las arterias se obtuvieron de ratas Wistar macho y se colocaron en cámaras para tejido aislado para perfundirse in vitro con distintas concentraciones de insulina y estrógenos estimulando la contracción con KCl 40 mmol/L. La insulina elevó la fuerza de la contracción inducida por KCl. Este incremento desapareció cuando se eliminó el endotelio. El E2β disminuyó la tensión desarrollada por las arterias conforme se aumentó la dosis y el efecto desapareció al quitar el endotelio. El incremento en la tensión por insulina disminuyó con E2β. En conclusión el efecto de la insulina sobre las arterias femorales y coronarias se encuentra modulado por el E2β.(Arch Cardiol Mex 2003; 73:254-260).
Subject(s)
Animals , Male , Rats , Estradiol/physiology , Insulin/pharmacology , Muscle Contraction/drug effects , Muscle Contraction/physiology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/physiology , Rats, WistarABSTRACT
El propósito de esta revisión es analizar las diferentes rutas metabólicas utilizadas por el corazón en momentos del desarrollo y situaciones como la hipoxia y la enfermedad, para tratar de comprenderlas y utilizarlas para restablecer las condiciones normales en células que se encuentran comprometidas durante un infarto.
We describe different metabolic states of the heart, during developmental stages, hypoxia and illness, to understand and use them to try to reestablish the normal conditions. (Arch Cardiol Mex 2003; 73:218-229).