RESUMO
BACKGROUND: Arteriogenesis is a process whereby collateral vessels remodel usually in response to increased blood flow and/or wall stress. Remodeling of collaterals can function as a natural bypass to alleviate ischemia during arterial occlusion. Here we used a genetic approach to investigate possible roles of tyrosine receptor c-Kit in arteriogenesis. METHODS: Mutant mice with loss of c-Kit function (KitW/W-v), and controls were subjected to hindlimb ischemia. Blood flow recovery was evaluated pre-, post-, and weekly after ischemia. Foot ischemic damage and function were assessed between days 1 to 14 post-ischemia while collaterals remodeling were measured 28 days post-ischemia. Both groups of mice also were subjected to wild type bone marrow cells transplantation 3 weeks before hindlimb ischemia to evaluate possible contributions of defective bone marrow c-Kit expression on vascular recovery. RESULTS: KitW/W-v mice displayed impaired blood flow recovery, greater ischemic damage and foot dysfunction after ischemia compared to controls. KitW/W-v mice also demonstrated impaired collateral remodeling consistent with flow recovery findings. Because arteriogenesis is a biological process that involves bone marrow-derived cells, we investigated which source of c-Kit signaling (bone marrow or vascular) plays a major role in arteriogenesis. KitW/W-v mice transplanted with bone marrow wild type cells exhibited similar phenotype of impaired blood flow recovery, greater tissue ischemic damage and foot dysfunction as nontransplanted KitW/W-v mice. CONCLUSION: This study provides evidence that c-Kit signaling is required during arteriogenesis. Also, it strongly suggests a vascular role for c-Kit signaling because rescue of systemic c-Kit activity by bone marrow transplantation did not augment the functional recovery of KitW/W-v mouse hindlimbs.
Assuntos
Circulação Colateral/fisiologia , Membro Posterior/irrigação sanguínea , Isquemia/fisiopatologia , Neovascularização Fisiológica/fisiologia , Proteínas Proto-Oncogênicas c-kit/deficiência , Animais , Biomarcadores/metabolismo , Transplante de Medula Óssea , Membro Posterior/fisiologia , Membro Posterior/fisiopatologia , Isquemia/metabolismo , Isquemia/terapia , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-kit/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: There are few data about the epidemiology of acute anterior uveitis (AAU) from Latin America. In Cuba, the genetic admixture of the population could modify the HLA-B27-AAU association. In this study, the authors compared the distribution of the HLA-B27 allele in patients and controls and described some clinical outcomes. MATERIALS AND METHODS: The clinical features of patients were collected from their medical records. HLA-B27 genotyping was performed using the polymerase chain reaction. HLA-B27 allele distribution was compared between patients and controls. RESULTS: HLA-B27 allele was present in 55.4% of the patients and 0.87% of the controls. AAU HLA-B27 positivity was associated with males, frequent episodes, and a systemic disease. There is no difference in ocular complications between HLA-B27-positive and -negative patients. CONCLUSIONS: Results from this study are similar to data described in other countries. HLA-B27 allele distribution in controls is lower than other reports in Caucasian populations.