RESUMO
Conjugated linoleic acid (CLA) has the unique property of inducing regression of pre-established murine atherosclerosis. Understanding the mechanism(s) involved may help identify endogenous pathways that reverse human atherosclerosis. Here, we provide evidence that CLA inhibits foam cell formation via regulation of the nuclear receptor coactivator, peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α, and that macrophage PGC-1α plays a role in atheroprotection in vivo. PGC-1α was identified as a hub gene within a cluster in the aorta of the apoE(-/-) mouse in the CLA-induced regression model. PGC-1α was localized to macrophage/foam cells in the murine aorta where its expression was increased during CLA-induced regression. PGC-1α expression was also detected in macrophages in human atherosclerosis and was inversely linked to disease progression in patients with the disease. Deletion of PGC-1α in bone marrow derived macrophages promoted, whilst over expression of the gene inhibited foam cell formation. Importantly, macrophage specific deletion of PGC-1α accelerated atherosclerosis in the LDLR(-/-) mouse in vivo. These novel data support a functional role for PGC-1α in atheroprotection.
Assuntos
Aterosclerose/fisiopatologia , Células Espumosas/efeitos dos fármacos , Ácidos Linoleicos Conjugados/metabolismo , Fatores de Transcrição/metabolismo , Animais , Aorta/fisiopatologia , Células Cultivadas , Deleção de Genes , Expressão Gênica , Humanos , Camundongos , Camundongos Knockout , Coativador 1-alfa do Receptor gama Ativado por Proliferador de PeroxissomoAssuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Prótese Vascular/efeitos adversos , Oclusão de Enxerto Vascular/etiologia , Isquemia/etiologia , Extremidade Inferior/irrigação sanguínea , Falha de Prótese , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aortografia/métodos , Implante de Prótese Vascular/instrumentação , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/cirurgia , Humanos , Isquemia/diagnóstico por imagem , Isquemia/cirurgia , Desenho de Prótese , Reoperação , Tomografia Computadorizada por Raios XRESUMO
A woman aged 75 years developed chylous ascites day 5 after emergency abdominal aortic aneurysm repair. She was still on artificial ventilation at the time of diagnosis. The first symptoms were high ventilation pressure, an elevated diaphragm, and abdominal distention. The patient was treated conservatively with drainage and total parenteral nutrition and given tube feeding without long-chain triglycerides. Unfortunately, the patient died of sepsis on day 25. Chylous ascites is an unusual complication of retroperitoneal surgery. Abdominal paracentesis is a simple means to confirm the diagnosis. Initial treatment consists of draining the chylus and a medium-chain triglyceride diet or total parenteral nutrition. When this fails, more invasive treatment is required, consisting of direct lymphatic repair or peritoneovenous shunting. In mechanically ventilated patients, gradually progressive symptoms of abdominal hypertension after surgery in the retroperitoneal space should arouse suspicion of this complication.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Ascite Quilosa/etiologia , Complicações Pós-Operatórias , Idoso , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Ruptura Aórtica/complicações , Ruptura Aórtica/diagnóstico por imagem , Ascite Quilosa/diagnóstico por imagem , Ascite Quilosa/terapia , Drenagem , Emergências , Nutrição Enteral , Evolução Fatal , Feminino , Humanos , Nutrição Parenteral Total , Pneumonia/complicações , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/terapia , Tomografia Computadorizada por Raios XRESUMO
A 78-year-old woman presented with a gastrointestinal hemorrhage and palpable abdominal aortic aneurysm. The computed tomography scan of the abdomen showed a primary aortoenteric fistula. The challenging clinical diagnosis of aortoenteric fistulae and their surgical treatment options are discussed.