RESUMEN
Aliskiren is an oral antihypertensive medication that acts by directly inhibiting renin. High levels of circulating renin and prorenin activate the pathological signaling pathway of fibrosis. This drug also reduces oxidative stress. Thus, the aim of this systematic review is to analyze experimental studies that show the actions of aliskiren on fibrosis. PubMed and LILACS databases were consulted using the keywords aliskiren and fibrosis within the period between 2005 and 2017. Fifty-three articles were analyzed. In the heart, aliskiren attenuated remodeling, hypertrophy, inflammatory cytokines, collagen deposition, and oxidative stress. In the kidneys, there was a reduction in interstitial fibrosis, the infiltration of inflammatory cells, apoptosis, proteinuria, and in the recruitment of macrophages. In diabetic models, an improvement in the albumin/creatinine relationship and in the insulin pathway in skeletal muscles was observed; aliskiren was beneficial to pancreatic function and glucose tolerance. In the liver, aliskiren reduced fibrosis, steatosis, inflammatory cytokines, and collagen deposition. In the lung and peritoneal tissues, there was a reduction in fibrosis. Many studies have reported on the beneficial effects of aliskiren on endothelial function and arterial rigidity. A reduction in fibrosis in different organs is cited by many authors, which complies with the results found in this review. However, studies diverge on the use of the drug in diabetic patients. Aliskiren has antifibrotic potential in several experimental models, interfering with the levels of fibrogenic cytokines and oxidative stress. Therefore, its use in diseases in which fibrosis plays an important pathophysiological role is suggested.
Asunto(s)
Amidas/administración & dosificación , Fibrosis Endomiocárdica/tratamiento farmacológico , Fumaratos/administración & dosificación , Nefritis Intersticial/tratamiento farmacológico , Amidas/farmacología , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad , Reposicionamiento de Medicamentos , Fibrosis Endomiocárdica/inmunología , Fibrosis Endomiocárdica/patología , Fibrosis , Fumaratos/farmacología , Humanos , Nefritis Intersticial/inmunología , Nefritis Intersticial/patología , Estrés Oxidativo/efectos de los fármacosRESUMEN
Heart failure (HF) is a cardiovascular syndrome characterized by maladaptive changes with an underlying inflammatory mediated pathogenesis. Nevertheless, current therapy is aimed at the heart workload and neurohormonal axis; thus, prognosis remains poor. To continue improving treatment, we rely on murine models for a better understanding of HF pathophysiology. Among them, pressure overload HF (PO-HF) animal models are a common strategy. Development of PO-HF is characterized by monocyte infiltration, which orchestrates a cascade of events leading to sustained inflammation and maladaptive changes. Here, we divide the PO-HF model progression into four phases and describe the inflammatory, structural, and gene expression profiles. This division is relevant due to its similarities with clinical hypertensive heart disease progression to HF. Evidence shows improvement in hemodynamic and other local parameters by altering the inflammatory response in a specific immune response at a specific point of time. Thus, it is relevant to focus on the time-dependent immune response interaction in order to provide more effective therapy. This review summarizes the pathogenesis of PO-HF murine models, highlighting the inflammatory events in a time frame view. By this approach, we expect to provide researchers with a better understanding of the intertwining time-dependent events that occur in PO-HF.
Asunto(s)
Linfocitos B/inmunología , Insuficiencia Cardíaca/inmunología , Hipertensión/inmunología , Monocitos/inmunología , Linfocitos T/inmunología , Angiotensina II/administración & dosificación , Angiotensina II/efectos adversos , Animales , Aorta/inmunología , Aorta/patología , Linfocitos B/patología , Cardiomegalia/inmunología , Cardiomegalia/patología , Movimiento Celular , Constricción Patológica/inmunología , Constricción Patológica/patología , Citocinas/biosíntesis , Citocinas/inmunología , Modelos Animales de Enfermedad , Fibrosis Endomiocárdica/inmunología , Fibrosis Endomiocárdica/patología , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/patología , Humanos , Hipertensión/complicaciones , Hipertensión/patología , Ratones , Monocitos/patología , Linfocitos T/patología , Factores de Tiempo , Disfunción Ventricular Izquierda/inmunología , Disfunción Ventricular Izquierda/patologíaRESUMEN
Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi. The immune system plays an important role in the reduction of parasite load, but may also contribute to the development of lesions observed during the chronic phase of the disease. We analyzed cytokines produced by inflammatory heart cells in 21 autopsy samples obtained from patients with Chagas' disease divided according to the presence or absence of heart failure (HF). Left ventricular sections were analyzed by immunohistochemistry using antibodies against human IL-4, IFN-γ, TGF-ß, TNF-α, and NOS2. In situ mRNA expression was quantified by a Low Density Array. The number of IFN-γ-positive cells was significantly higher than IL-4 positive cells. TNF-α, TGF-ß and NOS2 were detected in 65%, 62% and 94% of samples respectively. There was an association between TNF-α-producing cells and the presence of HF. Subjects with HF presented higher levels of STAT4 mRNA, whereas FoxP3 and STAT6 levels were similar in the two groups. A Th1 cytokine pattern predominated in the cardiac inflammatory cell infiltrate of Chagas' disease patients associated with HF. High degree of fibrosis was associated with low NOS2 expression. These results support the idea that Th1 immune responses are involved in heart lesions of Chagas' disease patients.