Endothelial Dysfunction: Clinical Implications in Cardiovascular Disease and Therapeutic Approaches

Atherosclerosis is a chronic progressive vascular disease. It starts early in life, has a long asymptomatic phase, and a progression accelerated by various cardiovascular risk factors. The endothelium is an active inner layer of the blood vessel. It generates many factors that regulate vascular tone, the adhesion of circulating blood cells, smooth muscle proliferation, and inflammation, which are the key mechanisms of atherosclerosis and can contribute to the development of cardiovascular events. There is growing evidence that functional impairment of the endothelium is one of the first recognizable signs of development of atherosclerosis and is present long before the occurrence of atherosclerotic cardiovascular disease. Therefore, understanding the endothelium's central role provides not only insights into pathophysiology, but also a possible clinical opportunity to detect early disease, stratify cardiovascular risk, and assess response to treatments. In the present review, we will discuss the clinical implications of endothelial function as well as the therapeutic issues for endothelial dysfunction in cardiovascular disease as primary and secondary endothelial therapy.

Nitric oxide and immune response.

Nitric oxide (NO), initially described as a physiological mediator of endothelial cell relaxation plays an important role in hypotension. It is an intercellular messenger and has been recognized as one of the most versatile players in the immune system. Cells of the innate immune system--macrophages, neutrophils and natural killer (NK) cells use pattern recognition receptors to recognize molecular patterns associated with pathogens. Activated macrophages then inhibit pathogen replication by releasing a variety of effector molecules, including NO. In addition to macrophages, a large number of other immune system cells produce and respond to NO. Thus, NO is important as a toxic defense molecule against infectious organisms. It also regulates the functional activity, growth and death of many immune and inflammatory cell types including macrophages, T lymphocytes, antigen-presenting cells, mast cells, neutrophils and NK cells. However, the role of NO in non-specific and specific immunity in vivo and in immunologically mediated diseases and inflammation is poorly understood. This review discusses the role of NO in immune response and inflammation and its mechanisms of action in these processes.

Estudo da interação entre células endoteliais humanas e biomateriais utilizados em cirurgia buco-maxilo-facial / Interaction of human endothelial cells with biomaterials applied on maxillo-facial surgery

Neste estudo procuramos analisar a interação entre células endoteliais humanas e biomateriais utilizados em cirurgia oral, através de análises histológicas e ensaios imunocitoquímicos. Culturas primárias foram isoladas de veias de cordões umbilicais humanos. As células foram semeadas, em densidade determinada, sobre secções circulares de membrana colágena, placas de titânio e controles; foram mantidas por 1, 7 ou 14 dias. As células proliferaram, atingiram confluência e após 14 dias formaram camada plana e uniforme. Os resultados demonstraram que os materiais estudados permitem a proliferação e a adesão das células endoteliais. Esta adesão é mediada pela interação de integrinas e proteínas.With the present investigation, we examined the behavior of endothelial cells on two different biomaterials, using histological and immunocitochemical methods. The endothelial cells were isolated from umbilical cord veins. Cells, after two passages, were seeded in a standard density on a collagen membrane, on commercially pure titanium in the form of plates and on control surfaces. Then these were maintained for 1, 7 or 14 days. After 14 days, we could observe a confluent monolayer of cells. Our results showed that both studied materials support endothelial cells growth and attachment and this is most related to the binding through integrins and proteins...

Expression of ICAM-1 on the Hantaan virus-infected human umbilical vein endothelial cells

OBJECTIVES: In HFRS, there is a varying degree of disseminated intravascular coagulation which was evident in the early phase of the illness. It is believed also that DIC would be the consequence, at least in part, of functional changes of endothelium resulting in kinin activation and clinical syndrome. This study investigated the role of adhesion molecule in the pathogenesis of Hantaan virus-related disease. METHODS: The expression of ICAM-1 antigen on the cell membrane of human umbilical vein endothelial cells was assessed by immunohistochemistry, and ICAM-1 mRNA in the endothelial cells was assessed by in situ hybridization after Hantaan virus infection (2.6 x 10(4) PFU/mL) with the time course. RESULTS: In immunohistochemistry, the number of ICAM-1 positive cells increased with time during the 12 or 24 hours after infection. 5 to 10% of HUVECs had been positive after 12-24 hours and the number of positive cells decreased abruptly after 24 hours. Hantaan antigen had been noticed after 12 hours focally on the HUVECs but continued to proliferate into day 7 post-infection when most of HUVECs were infected by Hantaan virus. In situ hybridization showed identical patterns of ICAM-1 mRNA expression after Hantaan virus infection. CONCLUSION: It implies that the Hantaan virus infection on HUVECs would express more ICAM-1 on their surface and implicated in the pathogenesis of early clinical syndrome of HFRS.

Behcet's disease sera containing antiendothelial cell antibodies promote adhesion of T lymphocytes to cultured human dermal microvascular endothelial cells

Antiendothelial cell antibodies (AECA) have been detected in the sera of patients of autoimmune diseases showing vasculitis. Using IgM-ELISA, we found AECA in 42 (56%) of 75 sera samples from patients with Behcet's disease in a previous study. All of the 15 AECA-positive sera of Behcet's disease patients had an increased expression of the intercellular cell adhesion molecule-1 (ICAM-1), 93.3% of the sera induced the vascular cell adhesion molecule-1 (VCAM-1), and 100% of the serum induced the E-selectin molecule on human dermal microvascular endothelial cells (HDMEC). After stimulation of HDMEC with AECA-positive sera of Behcet's disease patients, the expression of ICAM-1 and VCAM-1 on HDMEC increased significantly at 4 hours, reaching a peak at 16 hours. Expression of E-selectin was induced at 1 hour after stimulation with a peak at 4 hours and it decreased thereafter. Adherence of T lymphocytes to HDMEC increased significantly after stimulation with AECA-positive sera from Behcet's disease patients. Also, the adherence of T lymphocytes to HDMEC increased at 4 hours and returned to its normal level at 48 hours. These results show that AECA-positive sera of Behcet's disease patients are capable of activating HDMEC to promote the adherence of T lymphocytes to increase the expression of ICAM-1, VCAM-1, and E-selectin on the cell surfaces. The whole process may play an important role in the pathogenesis of vasculitis in Behcet's disease.

Fator von Willebrand e disfunçäo endotelial pulmonar. Implicaçöes prognósticas / von Willebrand factor and pulmonary vascular endothelial cell dysfunction. Prognostic implications

OBJETIVO - Avaliar alteraçöes quantitativas e estruturais do fator von Willebrand (fvW) circulante em 40 pacientes com hipertensäo pulmonar pré-capilar e verificar possíveis implicaçöes prognósticas dos resultados iniciais, em um ano de seguimento. MÉTODOS - A atividade antigênica plasmática do fator von Willebrand (vWF:Ag) foi analisada por imunoeletroforese. A concentraçäo de multímeros de baixo peso molecular em relaçäo...

Immunological graft rejection and the vascular endothelial cell

Rejection is still the major cause of organ loss in transplantation. This process involves an immune response of the patient (recipient) against hystocompatibility antigens of the donor, present in the transplanted organ. Nevertheless, improvements in the evaluation of the humoral status of recipients and new immunosuppressive therapies have brought new insights into the factors involved in early rejection. Another important area in transplantation immunology is the participation of vascular endothelial cells, either as targets or as active agents of the rejection process. Humoral responses against antigens specific to endothelial cells, and absent in lymphocytes, have been associated with acute graft loss. These different aspects of transplant rejection are discussed.