RESUMO
BACKGROUND: The cytokine interleukin (IL)-1 is an important mediator of inflammation and cardiovascular disease. Activity of this cytokine is modulated endogenously via the IL-1 receptor antagonist (IL-1Ra). The role of IL-1Ra in neointima formation after injury, however, is poorly understood. METHODS AND RESULTS: Using IL-1Ra-deficient (IL-1Ra-/-; backcrossed 8 generations into the C57BL/6J background) and wild-type (IL-1Ra+/+) mice, we investigated neointimal formation 3 weeks after femoral artery injury induced by an external vascular cuff model. Intima and media thicknesses were measured, and the intima/media ratio was calculated. The mean intimal thickness and the intima/media ratio of IL-1Ra-/- mice increased by 249% (31.8+/-2.9 microm [n=10] versus 9.1+/-0.7 microm [n=10]; P<0.0001) and 257% (2.5+/-0.2 versus 0.7+/-0.1; P<0.0001), respectively, compared with IL-1Ra+/+ mice. No significant differences were observed in the medial thickness. Control immunostaining for IL-1Ra in injured vessels localized IL-1beta and the endogenous inhibitor in the endothelium and inflammatory cells of the adventitia in IL-1Ra+/+ but not IL-1Ra-/- mice. CONCLUSIONS: The absence of IL-1Ra promotes neointimal formation in mice after injury. These results suggest that endogenous IL-1Ra may suppress other occlusive vascular responses to injury, such as atherosclerosis and restenosis after angioplasty.
Assuntos
Artéria Femoral/lesões , Artéria Femoral/patologia , Sialoglicoproteínas/deficiência , Túnica Íntima/lesões , Túnica Íntima/patologia , Animais , Divisão Celular/genética , Modelos Animais de Doenças , Progressão da Doença , Artéria Femoral/metabolismo , Predisposição Genética para Doença , Homozigoto , Hiperplasia/patologia , Imuno-Histoquímica , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Fenótipo , Antígeno Nuclear de Célula em Proliferação/biossíntese , Sialoglicoproteínas/biossíntese , Sialoglicoproteínas/genética , Túnica Íntima/metabolismoRESUMO
OBJECTIVE: We aimed to establish an enzyme-linked immunosorbent assay for measuring soluble elastin fragments (sELAF) in serum and to reveal its usefulness in diagnosing acute aortic dissection (AAD). METHODS AND RESULTS: An enzyme-linked immunosorbent assay to measure sELAF in serum was developed by using the newly created double monoclonal antibodies, which recognize the different epitopes of human aortic elastin. Twenty-five AAD patients, 50 patients with acute myocardial infarction (AMI), and 474 healthy individuals were enrolled in the study. The sELAF levels from healthy subjects gradually increased with aging. When the cutoff point for positivity was set at the mean+3 SD (ie, 3 SD above the mean in healthy subjects at each age), 16 AAD patients (64.0%) were found be positive, whereas only 1 AMI patient was found to be positive (2.0%). AAD patients with either an open or a partially open pseudolumen were found be 88.9% positive for sELAF, whereas those with its early closure were 0% positive. The difference in the sELAF levels between AAD patients with and without a thrombotic closure of false lumen was significant (60.3+/-15.6 versus 135.4+/-53.2 ng/mL, respectively; P<0.005). CONCLUSIONS: The sELAF level in serum may be a useful marker for helping in the diagnosis and screening of AAD and may also help to distinguish AAD from AMI.