RESUMO
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.
Assuntos
Linfócitos B/imunologia , Insuficiência Cardíaca/imunologia , Hipertensão/imunologia , Monócitos/imunologia , Linfócitos T/imunologia , Angiotensina II/administração & dosagem , Angiotensina II/efeitos adversos , Animais , Aorta/imunologia , Aorta/patologia , Linfócitos B/patologia , Cardiomegalia/imunologia , Cardiomegalia/patologia , Movimento Celular , Constrição Patológica/imunologia , Constrição Patológica/patologia , Citocinas/biossíntese , Citocinas/imunologia , Modelos Animais de Doenças , Fibrose Endomiocárdica/imunologia , Fibrose Endomiocárdica/patologia , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Humanos , Hipertensão/complicações , Hipertensão/patologia , Camundongos , Monócitos/patologia , Linfócitos T/patologia , Fatores de Tempo , Disfunção Ventricular Esquerda/imunologia , Disfunção Ventricular Esquerda/patologiaRESUMO
When infected with Trypanosoma cruzi, Beagle dogs develop symptoms similar to those of Chagas disease in human beings, and could be an important experimental model for a better understanding of the immunopathogenic mechanisms involved in chronic chagasic infection. This study evaluates IL-10, IFN-gamma and TNF-alpha production in the sera, culture supernatant, heart and cervical lymph nodes and their correlation with cardiomegaly, cardiac inflammation and fibrosis in Beagle dogs infected with T. cruzi. Pathological analysis showed severe splenomegaly, lymphadenopathy and myocarditis in all infected dogs during the acute phase of the disease, with cardiomegaly, inflammation and fibrosis observed in 83% of the animals infected by T. cruzi during the chronic phase. The data indicate that infected animals producing IL-10 in the heart during the chronic phase and showing high IL-10 production in the culture supernatant and serum during the acute phase had lower cardiac alterations (myocarditis, fibrosis and cardiomegaly) than those with high IFN-gamma and TNF-alpha levels. These animals produced low IL-10 levels in the culture supernatant and serum during the acute phase and did not produce IL-10 in the heart during the chronic phase of the disease. Our findings showed that Beagle dogs are a good model for studying the immunopathogenic mechanism of Chagas disease, since they reproduce the clinical and immunological findings described in chagasic patients. The data suggest that the development of the chronic cardiac form of the disease is related to a strong Th1 response during the acute phase of the disease, while the development of the indeterminate form results from a blend of Th1 and Th2 responses soon after infection, suggesting that the acute phase immune response is important for the genesis of chronic cardiac lesions.
Assuntos
Cardiomiopatia Chagásica/veterinária , Doenças do Cão/parasitologia , Interferon gama/biossíntese , Interleucina-10/biossíntese , Trypanosoma cruzi/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Animais , Cardiomegalia/imunologia , Cardiomegalia/parasitologia , Cardiomiopatia Chagásica/imunologia , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/patologia , Modelos Animais de Doenças , Doenças do Cão/imunologia , Doenças do Cão/patologia , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Fibrose/imunologia , Fibrose/parasitologia , Histocitoquímica/veterinária , Interferon gama/sangue , Interferon gama/genética , Interferon gama/imunologia , Interleucina-10/sangue , Interleucina-10/genética , Interleucina-10/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Esplenomegalia/imunologia , Esplenomegalia/parasitologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
A systematic study following infection by various strains of the protozoan parasite, Trypanosoma cruzi, and the simultaneous monitoring of the humoral immune response together with the elicited cellular response, could add greatly to our understanding of differences between strains of this important human pathogen. In that sense, acute and chronic infections with distinct T. cruzi strains (Y, Berenice-78 and ABC) in Beagle dogs were studied through a longitudinal evaluation of immunoglobulin G (IgG), IgG1 and IgG2 isotypes (by ELISA and flow cytometry (FC)), as well as measurements of peripheral blood mononuclear cell (PBMC) proliferation over a 100-week period, and their correlation with cardiomegaly. Our results show that infected animals presenting cardiomegaly showed lower or absent levels of IgG1 during the chronic phase of the infection, when compared to those that did not show an increase in heart weight. In that manner, our results suggest that IgG1 could be used as a marker for cardiac pathogenicity in Chagas disease.
Assuntos
Cardiomegalia/imunologia , Cardiomegalia/parasitologia , Doença de Chagas/veterinária , Doenças do Cão/imunologia , Doenças do Cão/parasitologia , Imunoglobulina G/imunologia , Trypanosoma cruzi/imunologia , Animais , Anticorpos Antiprotozoários/sangue , Processos de Crescimento Celular/imunologia , Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Citometria de Fluxo/veterinária , Imunoglobulina G/sangue , Cinética , Leucócitos Mononucleares/imunologia , Tamanho do Órgão , Análise de RegressãoAssuntos
Anticorpos/análise , Cardiomiopatia Chagásica/imunologia , Doença de Chagas/imunologia , Endotélio/imunologia , Nervos Periféricos/imunologia , Adulto , Cardiomegalia/imunologia , Feminino , Bloqueio Cardíaco/imunologia , Insuficiência Cardíaca/imunologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Antibodies to cow-heart tissue were prepared in mice. These antibodies were used to demonstrate the presence of cardiac antigens in sera of patients with cardiac disease. Normal individuals gave positive reactions, but to a lesser extent (AU)