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Abstract: Background: The objective of this study was to determine the effects of pentraxin3 (PTX3) on human oxidized low density lipoprotein (oxLDL) uptake and cholesterol efflux from human macrophage foam cells, which may play a critical role in atherogenesis. Methods: The effects of PTX3 on oxLDL uptake and cholesterol efflux were determined after transfection of human THP-1 macrophages with pSG5hPTX3 or PTX3siRNA plasmids. To evaluate the role of specific signaling pathways, human THP-1 cells were pre-treated with inhibitors of the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), phosphatidylinositide 3-kinases (PI3-K), and p38 mitogen-activated protein kinase (MAPK) pathways (PD98059, LY294002, and SB203580, respectively), and then exposed to oxLDL for the uptake assay or oxLDL and [3H]-cholesterol and apolipoprotein A-I (apoA-I) for the cholesterol efflux assay. Results: PTX3 overexpression not only promoted oxLDL uptake but also significantly reduced cholesterol efflux to apoA-I; it also significantly decreased the expression of peroxisome proliferator-activated receptor-γ (PPARγ), liver X receptor alpha (LXRα) and ATP-binding membrane cassette transporter A-1 (ABCA1), which was increased with PTX3 silencing. Furthermore, PTX3 significantly increased p-ERK1/2 levels in THP-1-derived foam cells, and inhibition of ERK1/2 by PD98059 significantly reduced the oxLDL uptake and promoted the cholesterol efflux induced by PTX3 overexpression. Conclusion: Here, we demonstrate that PTX3 affects lipid accumulation in human macrophages, increasing oxLDL uptake and inhibiting cholesterol efflux. That is the underlying possible mechanisms of PTX3 contribution to the progression of atherosclerosis. [Copyright &y& Elsevier]

Abstract: Background: Bone mesenchymal stem cells (BMSCs) are attractive candidates for cell based therapies to cardiovascular disease such as infarction and atherosclerosis; however, the mechanisms responsible for stem cell chemotaxis and homing remain unknown. Chemokine stromal cell-derived factor 1 (SDF-1α) is involved in the process of atherogenesis. This study was aimed at investigating whether the SDF-1α of human umbilical vein endothelial cells (HUVECs) plays a role in migration of BM-derived CXCR4+(receptor for SDF-1α) stem cells. Methods: HUVECs were cultured from human umbilical cords and was treated with ox-LDL. The mRNA and protein expression of SDF-1α was detected in HUVECs. CXCR4+BMSCs from bone marrow were isolated and were tested by migration and adhesion assays. Results: It was found that ox-LDL induced HUVECs to increase the mRNA and protein expression of SDF-1α. Ox-LDL increased the migratory and adhesion response of CXCR4+BMSCs. When the neutralizing SDF-1α antibody abrogated the secreted SDF-1α, the migration and adhesion response of CXCR4+BMSCs markedly decreased. Conclusions: Our data indicated that the endothelial cells (ECs) stimulated by ox-LDL could increase the BMSCs migratory response via SDF-1α/CXCR4 signaling axis. These findings provide a new paradigm for biological effects of ox-LDL and have implications for novel stem cell therapeutic strategies for atherosclerosis. [Copyright &y& Elsevier]