Effect of low-density lipoprotein apheresis on circulating endothelial progenitor cells in familial hypercholesterolemia.

BACKGROUND: Long-term treatment with low-density lipoprotein (LDL) apheresis (LA) has been shown to reduce the incidence of cardiovascular events in patients affected by familial hypercholesterolemia (FH). Data from experimental studies suggest that circulating endothelial progenitor cells (EPCs) can repair the vascular lesions caused by atherosclerosis. Since a reduction of these cells has been demonstrated to predict atherosclerosis progression, the aim of this study was to verify whether LA can increase the percentage of EPCs. METHODS: In 15 patients affected by FH periodically treated with LA, the percentage of EPCs was determined before and after performing LA, and compared with the values of 15 control subjects and 15 hypercholesterolemic patients treated with statins. RESULTS: Significant differences were found in FH patients between the pre-apheresis percentages of CD34+/KDR+, defined as EPCs by a wide consensus of opinion, and the values found 24 h after the procedures (0.00868 +/- 0.003 vs. 0.01009 +/- 0.002%, p < 0.005). Instead, the percentages of CD34+/KDR+/CD133+, considered as an immature subset of EPCs, remained substantially unchanged. However, a significant reduction in the percentage of EPCs was observed in both patient groups as compared to the controls, at all the assessment times. CONCLUSION: In the short-term LA seems to stimulate mobilization of CD34+/KDR+ cells. Hypercholesterolemic patients show a lower percentage of EPCs than controls. There were no differences in the EPCs percentages between the 2 patients groups, despite the fact that LDL cholesterol levels were higher in the group undergoing LA.

Cytokine/Chemokine HLDA8 Workshop panel report: analysis of receptors on lymphocytes from cord blood, normal and asthmatic subjects, and HIV positive patients.

Chemokines and cytokines are involved in many processes, both physiological and pathological, particularly the recruitment, differentiation, activation, and proliferation of immune cells taking part in ontogenesis, inflammation, and cancer. It was assumed that chemokines and cytokines receptors are expressed in a regulated manner by human lymphocytes during ontogeny and later on, under the environmental stimulation of antigens they contribute to organogenesis, angiogenesis, and tissue remodeling, as well as modulating leukocyte effector functions. Using monoclonal antibodies classified by the Cytokine/Chemokine section of the 8th International Workshop on Human Leukocyte Differentiation Antigens, we analyzed human lymphocytes in blood samples drawn from the umbilical cord, normal adults, allergic and non-allergic asthma patients, HIV infected, and AIDS positive subjects. The main differences noted between adult and cord blood lymphocytes were related to CCR7 and CXCR4 receptors, which were more strongly expressed on cord blood lymphocytes, confirming the important role of these chemokines during development of the immune system. As with the HIV, CXCR4, and CCR5 co-receptors, we found no differences in CXCR4 expression between HIV and AIDS patients. However CCR5 was more strongly expressed in AIDS patients, which is likely to be associated with the evolution of disease. Further studies are needed to gain a better understanding of the functions of these molecules in the underlying pathogenesis of many diseases and to probe the use of the chemokine receptors as targets for therapeutic intervention.

Role of cytokines in gonarthrosis and knee prosthesis aseptic loosening.

Cytokines, which have been demonstrated in synovial fluids during various joint diseases, play an important role in mediating synovial inflammation and in regulating the immune response of many inflammatory processes. We studied synovial fluid, serum, and synovial fragments obtained from 33 patients--10 affected by serious gonarthrosis re-quiring a prosthetic implant, 8 with knee prosthesis aseptic loosening, and (as controls) 15 affected by degenerative meniscopathies--to evaluate the degree of inflammation and level of interleukins (IL-2, IL-4, IL-6, IL-10) and interferon gamma secretion. Histological analysis revealed slightly more infiltration by inflammatory cells in the synovial tissue of patients with gonarthrosis and knee prosthesis aseptic loosening than in that of the control group, with a high prevalence of macrophages. Moreover, we observed enhanced production of the studied cytokines, especially in synovial fluid as compared to serum, indicating that in the pathological conditions examined the inflammatory events are mainly localized. Because the role of these cytokines is to modulate inflammation, better knowledge of the involvement of cells and their soluble mediators in articular damage could guide immunomodulating treatment.