Assuntos
Infecções por Coronavirus/diagnóstico , Parto Obstétrico , Trabalho de Parto , Programas de Rastreamento/métodos , Admissão do Paciente , Pneumonia Viral/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico , Adulto , COVID-19 , Feminino , Humanos , Pandemias , Gravidez , Estudos RetrospectivosAssuntos
Infecções por Coronavirus , Coronavirus , Pandemias , Pneumonia Viral , Complicações Infecciosas na Gravidez , Betacoronavirus , COVID-19 , Feminino , Humanos , Gravidez , SARS-CoV-2RESUMO
Activation of the 5-lipoxygenase (5-LO) pathway leads to the biosynthesis of proinflammatory leukotriene lipid mediators. Genetic studies have associated 5-LO and its accessory protein, 5-LO-activating protein, with cardiovascular disease, myocardial infarction and stroke. Here we show that 5-LO-positive macrophages localize to the adventitia of diseased mouse and human arteries in areas of neoangiogenesis and that these cells constitute a main component of aortic aneurysms induced by an atherogenic diet containing cholate in mice deficient in apolipoprotein E. 5-LO deficiency markedly attenuates the formation of these aneurysms and is associated with reduced matrix metalloproteinase-2 activity and diminished plasma macrophage inflammatory protein-1alpha (MIP-1alpha; also called CCL3), but only minimally affects the formation of lipid-rich lesions. The leukotriene LTD(4) strongly stimulates expression of MIP-1alpha in macrophages and MIP-2 (also called CXCL2) in endothelial cells. These data link the 5-LO pathway to hyperlipidemia-dependent inflammation of the arterial wall and to pathogenesis of aortic aneurysms through a potential chemokine intermediary route.
Assuntos
Aneurisma da Aorta Abdominal/etiologia , Araquidonato 5-Lipoxigenase/metabolismo , Regulação da Expressão Gênica , Hiperlipidemias/complicações , Leucotrienos/biossíntese , Macrófagos/metabolismo , Proteínas Ativadoras de 5-Lipoxigenase , Análise de Variância , Animais , Western Blotting , Proteínas de Transporte/metabolismo , Quimiocina CCL2/sangue , Quimiocina CCL3 , Quimiocina CCL4 , Quimiocina CXCL1 , Quimiocinas CXC/metabolismo , Colatos , Tecido Conjuntivo/metabolismo , Citocinas/sangue , Primers do DNA , Dieta Aterogênica , Técnicas Histológicas , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Leucotrieno D4/metabolismo , Proteínas Inflamatórias de Macrófagos/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/metabolismo , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: Cells of adaptive immunity have been implicated in atherogenesis. Though substantial information is available on immune cells in atherosclerotic lesions of the lamina intima, cells in the lamina adventitia have received less attention. METHODS AND RESULTS: The composition of immune cells in the innominate artery and abdominal aorta was examined in young, adult, and old apolipoprotein (apo) E(-/-) and wild-type mice on standard mouse chow. In the innominate artery of apoE(-/-) mice, adventitial T cells increased at 32, 52, and 78 weeks exceeding those of the intima by 6-, 24-, and 85-fold. Single T cells dominated in young mice, later T/B cell clusters emerged, and lymphoid-like structures reminiscent of inflammatory follicles formed preferentially in the abdominal aorta of old mice. Follicles contained organized sets of immune response-regulating cells: Interdigitating dendritic cells, T cell effectors, proliferating B cells, and plasma cells. Adventitial T cell inflammation was associated with a marked increase in transcripts of the chemokine MIP-1alpha in the aorta but not in spleen or liver. CONCLUSIONS: Adventitial lymphocyte infiltration and formation of inflammatory follicle-like structures in the abdominal aorta of old apoE(-/-) mice point to the adventitia as a site of local adaptive immune reactions during atherogenesis in hyperlipidemic mice.