C-reactive protein decreases interleukin-8 production in human endothelial progenitor cells by inhibition of p38 MAPK pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>C-reactive protein (CRP) has been reported to damage the vascular wall by inducing endothelial dysfunction and inflammation, and it is also speculated to have a role in attenuating angiogenic functions of human endothelial progenitor cells (EPCs). Interleukin-8 (IL-8) is an important mediator of the paracrine mitogenic effect of EPCs, which has direct angiogenic effects on mature endothelial cells. We, herein, investigated the direct effect of CRP on IL-8 production and gene expression in cultured human EPCs.</p><p><b>METHODS</b>EPCs were isolated from the peripheral venous blood of healthy male volunteers. Cells were cultured in EndoCult liquid medium in the absence and presence of CRP at clinically relevant concentrations (5 to 25 microg/ml) for different durations (3 to 48 hours). IL-8 protein and mRNA of cultured EPCs were evaluated using ELISA and real-time PCR.</p><p><b>RESULTS</b>The results showed that CRP at a concentration of 10 microg/ml significantly reduced IL-8 secretion of cultured EPCs with a peak at 25 microg/ml, and also decreased mRNA expression in EPCs with a peak at 12 hours. In addition, preincubation of EPCs with SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK) decreased CRP inhibition of IL-8 mRNA expression at 12 hours in EPCs.</p><p><b>CONCLUSIONS</b>Our study, for the first time, demonstrates that CRP directly inhibits EPCs IL-8 secretion, a key cytokine player of angiogenesis induced by EPCs. Inhibition occurred in part via an effect of CRP to active the p38 MAPK signal transduction pathway in EPC. The ability of CRP to inhibit EPCs IL-8 secretion may represent an important mechanism that further links inflammation to cardiovascular disease.</p>

Autologous peripheral blood stem cell transplantation for the treatment of lower extremity arterial occlusive disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the safety and feasibility of autologous peripheral blood mononuclear cells (PBMNCs) implantation after granulocyte-colony stimulating factor (G-CSF)-induced mobilization in patients with lower extremity arterial occlusive disease (AOD).</p><p><b>METHODS</b>A total of 12 patients with AOD were enrolled in this study. Following administration of rhG-CSF (150 microg/d) for 5 days, PBMNCs were harvested and injected intramuscularly in the diseased extremities (3 x 10(9) per limb).</p><p><b>RESULTS</b>One patient received left leg amputation due to uncontrolled ulcer 15 days post PBMNCs transplantation and the symptoms and signs were improved significantly in 9 patients and the symptoms and signs remained unchanged in another 2 aged patients (> 70 years). Doppler ultrasonography measurement showed that peak systolic velocity in diseased extremities was significantly increased post transplantation [(44.55 +/- 4.13) cm/s vs. (21.32 +/- 0.63) cm/s, P < 0.01]. Contrast lower limb angiogram showed increased collateral vessels post transplantation. One aged patient (80 years) who did not respond to autologous PBMNCs received heterologous PBMNCs transplantation (PBMNCs was harvested from a young relative of him) 3 months post autologous PBMNCs transplantation and observed for another 3 months and all observed parameters improved significantly.</p><p><b>CONCLUSION</b>Implantation of autologous PBMNCs collected after G-CSF administration might offer a simple, safe, and effective therapy for the AOD patients.</p>