RESUMEN
The antithrombotic surface of endothelium is regulated in a coordinated manner. Tissue factor pathway inhibitor (TFPI) localized at the endothelial cell surface regulates the production of FXa by inhibiting the TF/VIIa complex. Systemic homozygotic deletion of the first Kunitz (K1) domain of TFPI results in intrauterine lethality in mice. Here we define the cellular sources of TFPI and their role in development, hemostasis, and thrombosis using TFPI conditional knockout mice. We used a Cre-lox strategy and generated mice with a floxed exon 4 (TFPI(Flox)) which encodes for the TFPI-K1 domain. Mice bred into Tie2-Cre and LysM-Cre lines to delete TFPI-K1 in endothelial (TFPI(Tie2)) and myelomonocytic (TFPI(LysM)) cells resulted in viable and fertile offspring. Plasma TFPI activity was reduced in the TFPI(Tie2) (71% ± 0.9%, P < .001) and TFPI(LysM) (19% ± 0.6%, P < .001) compared with TFPI(Flox) littermate controls. Tail and cuticle bleeding were unaffected. However, TFPI(Tie2) mice but not TFPI(LysM) mice had increased ferric chloride-induced arterial thrombosis. Taken together, the data reveal distinct roles for endothelial- and myelomonocytic-derived TFPI.
Asunto(s)
Células Endoteliales/metabolismo , Hemostasis , Lipoproteínas/sangre , Trombosis/sangre , Animales , Arterias/metabolismo , Arterias/patología , Femenino , Estimación de Kaplan-Meier , Lipoproteínas/genética , Lipoproteínas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Monocitos/citología , Monocitos/metabolismo , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptor TIE-2 , Trombosis/metabolismoAsunto(s)
Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/fisiopatología , Ecocardiografía Doppler , Pericarditis Constrictiva/diagnóstico por imagen , Pericarditis Constrictiva/fisiopatología , Adulto , Anciano , Velocidad del Flujo Sanguíneo/fisiología , Humanos , Masculino , Pericarditis Constrictiva/cirugía , Fenómenos Fisiológicos RespiratoriosRESUMEN
The exclusion of abdominal aortic aneurysms by endovascular techniques has enabled the treatment of patients who have high-risk comorbidities that preclude safe surgical repair. Since the development of the unibody bifurcated endovascular stent-graft for abdominal aortic aneurysm exclusion, remarkable technological improvements have facilitated stent-graft delivery and reduced the required size of the access site. Our initial institutional experience with the use of the Endologix IntuiTrak Express Delivery System for the Powerlink stent-graft (in 7 patients) shows that the device is suited for percutaneous use without sequelae. Herein, we describe the IntuiTrak system and the successful results of its use: we achieved percutaneous access and closure in all 7 patients, with no conversions to open repair or vascular exposure.