Late AEFs rarely occur during EVAR follow-up, but the risk is significantly increased when EVAR is performed for PSA after previous aortic surgery and EVAR is performed as an emergency. Conservative and surgical treatment of post-EVAR AEF are both associated with high mortality. However, beyond the perioperative period, surgical correction of AEFs appears to be durable at midterm follow-up.

Lymphatic endothelial cells (LECs) interact with different immune cells, including T cells within lymph nodes (LNs). However, direct interactions of LECs with immune cells have yet to be investigated. In vitro studies were performed to characterize primary cultures of human LECs derived from LNs in their capacity of interacting with T cells. The results show that LECs express HLA molecules and functional costimulatory molecules needed for T-cell activation. A direct binding of LECs and T cells was detected in cell cultures connected with a clustering of costimulatory molecules on the contact phase. LECs were also able to take up and process antigens. However, major histocompatibility complex class II(+) LECs fail to induce allogeneic T-cell proliferation. Interestingly, supernatants of IFN-γ activated LECs impair proliferation of T cells cocultured with allogeneic dendritic cells, suggesting an inhibitory role of LECs. Indoleamine 2,3 dioxygenase was identified as one inhibitory molecule, which may be responsible for the impaired CD4(+) T-cell proliferation. Our observations suggest a regulatory function for activated LECs on CD4(+) T cells, which may play a role in vivo in the maintenance of the critical balance between tolerance and recall responses.

Endothelial cells (ECs) are a site of human cytomegalovirus (HCMV) productive replication, haematogenous dissemination and persistence, and are assumed to play a critical role in the development of HCMV-associated vascular diseases. Although early reports have shown the presence of HCMV antigens and DNA in lymphoid tissues, the ability of HCMV to infect lymphatic ECs (LECs) has remained unaddressed due to the lack of a suitable in vitro system. This study provided evidence that a clinical isolate of HCMV (retaining its natural endotheliotropism) was able to productively infect purified lymph node-derived LECs and that it dysregulated the expression of several LEC genes involved in the inflammatory response to viral infection. Qualitative and quantitative analysis of virus-free supernatants from HCMV-infected LEC cultures revealed virus-induced secretion of several cytokines, chemokines and growth factors, many of which are involved in the regulation of EC physiological properties. Indeed, functional assays demonstrated that the secretome produced by HCMV-infected LECs stimulated angiogenesis in both LECs and blood ECs, and that neutralization of either interleukin (IL)-6 or granulocytemacrophage colony-stimulating factor (GM-CSF) in the secretome caused the loss of its angiogenic properties. The involvement of IL-6 and GM-CSF in the HCMV-mediated angiogenesis was further supported by the finding that the recombinant cytokines reproduced the angiogenic effects of the HCMV secretome. These findings suggest that HCMV induces haemangiogenesis and lymphangiogenesis through an indirect mechanism that relies on the stimulation of IL-6 and GM-CSF secretion from infected cells.

Objective— AIDS-related lymphomas are high grade and aggressively metastatic with poor prognosis. Lymphangiogenesis is essential in supporting proliferation and survival of lymphoma, as well as tumor dissemination. Data suggest that aberrant lymphangiogenesis relies on action of HIV-1 proteins rather than on a direct effect of the virus itself. HIV-1 matrix protein p17 was found to accumulate and persist in lymph nodes of patients even under highly active antiretroviral therapy. Because p17 was recently found to exert a potent proangiogenic activity by interacting with chemokine (C-X-C motif) receptors 1 and 2, we tested the prolymphangiogenic activity of the viral protein. Approach and Results— Human primary lymph node–derived lymphatic endothelial cells were used to perform capillary-like structure formation, wound healing, spheroids, and Western blot assays after stimulation with or without p17. Here, we show that p17 promotes lymphangiogenesis by binding to chemokine (C-X-C motif) receptor-1 and chemokine (C-X-C motif) receptor-2 expressed on lymph node–derived lymphatic endothelial cells and activating the Akt/extracellular signal–regulated kinase signaling pathway. In particular, it was found to induce capillary-like structure formation, sprout formation from spheroids, and increase lymph node–derived lymphatic endothelial cells motility. The p17 lymphangiogenic activity was, in part, sustained by activation of the endothelin-1/endothelin receptor B axis. A Matrigel plug assay showed that p17 was able to promote the outgrowth of lymphatic vessels in vivo, demonstrating that p17 directly regulates lymphatic vessel formation. Conclusions— Our results suggest that p17 may generate a prolymphangiogenic microenvironment and plays a role in predisposing the lymph node to lymphoma growth and metastasis. This finding offers new opportunities to identify treatment strategies in combating AIDS-related lymphomas.