Activation of formyl peptide receptor like-1 by serum amyloid A induces CCL2 production in human umbilical vein endothelial cells.
ABSTRACT We investigated the effects of serum amyloid A (SAA) on the production of C-C chemokine motif ligand 2 (CCL2) and the mechanism underlying SAA action in human umbilical vein endothelial cells (HUVECs). Stimulation of HUVECs by SAA elicited CCL2 production in a concentration-dependent manner. SAA induced the activations of NF-kappaB and AP-1, which were essential for CCL2 production after SAA stimulation. HUVECs expressed formyl peptide receptor-like 1 (FPRL1), and short interfering RNA knockdown of FPRL1 nearly completely blocked SAA-induced CCL2 production in HUVECs. We suggest that SAA stimulates CCL2 production via FPRL1 and, thus, contributes to atherosclerosis.
- SourceAvailable from: Shiro Kitamoto[show abstract] [hide abstract]
ABSTRACT: Monocyte infiltration into the arterial wall and its activation is the central event in atherogenesis. Thus, monocyte chemoattractant protein-1 (MCP-1) might be a novel therapeutic target against atherogenesis. We and others recently reported that blockade or abrogation of the MCP-1 pathway attenuates the initiation of atheroma formation in hypercholesterolemic mice. It remains unclear, however, whether blockade of MCP-1 can limit progression or destabilization of established lesions. We report here that blockade of MCP-1 by transfecting an N-terminal deletion mutant of the MCP-1 gene limited progression of preexisting atherosclerotic lesions in the aortic root in hypercholesterolemic mice. In addition, blockade of MCP-1 changed the lesion composition into a more stable phenotype, ie, containing fewer macrophages and lymphocytes, less lipid, and more smooth muscle cells and collagen. This strategy decreased expression of CD40 and the CD40 ligand in the atherosclerotic plaque and normalized the increased chemokine (RANTES and MCP-1) and cytokine (tumor necrosis factor alpha, interleukin-6, interleukin-1beta, and transforming growth factor beta(1)) gene expression. These data suggest that MCP-1 is a central mediator in the progression and destabilization of established atheroma. The results of the present study suggest that the inflammatory responses mediated by MCP-1 are important in atherosclerosis and its complications.Circulation 12/2002; 106(21):2700-6. · 15.20 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: A protein chemotactic for peripheral blood monocytes (SMC-CF) of potential importance in their recruitment to the arterial intima in atherogenesis was purified from serum-free medium conditioned by cultured baboon aortic medial smooth muscle cells. The purification of SMC-CF was monitored by a filter assay using human peripheral blood mononuclear cells and was achieved by batch separation on a cation-exchange gel followed by gel permeation chromatography, ion-exchange high-performance liquid chromatography (HPLC), and reversed-phase HPLC. The overall recovery was approximately 10% of the initial activity and yielded 0.5-1 microgram of SMC-CF/L of conditioned medium. On analytical sodium dodecyl sulfate-polyacrylamide gel electrophoresis, SMC-CF migrated as a monomeric protein with an apparent molecular weight of 14,500. A dose-dependent relationship was observed between SMC-CF concentration and monocyte chemotactic activity, with maximal and half-maximal biologic activity being observed at approximately 5 and 0.1 nM, respectively. Cultured baboon aortic smooth muscle cells also express the genes for both the A and B polypeptide chains of platelet-derived growth factor, which has been reported to be chemotactic for blood monocytes and neutrophils [Deuel, T. F., Senior, R. M., Huang, J. S., & Griffin, G. L. (1982) J. Clin. Invest. 69, 1046-1049]. Amino acid composition analyses indicate that SMC-CF is not derived either from polypeptide chain of this growth factor or from certain potentially chemotactic connective tissue proteins.Biochemistry 06/1988; 27(11):4162-8. · 3.38 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Inflammation long has been recognized as a hallmark of atherosclerotic lesions, but more recently attention has focused on chronic low-level elevations of specific plasma inflammatory proteins such as C-reactive protein (CRP) and serum amyloid A (SAA), which may not only represent markers of atherosclerosis risk but also participate directly in atherogenesis. This article briefly reviews evidence for and against potential roles of CRP as an atherosclerosis risk marker and in athero-genesis. The remainder of the article focuses on SAA, an inflammatory protein that is carried on, and may fundamentally alter the function of, high-density lipoprotein. Data are reviewed regarding the regulation of SAA by dietary cholesterol, obesity, and insulin resistance, and its potential role as an atherosclerosis mediator. Lying at the intersection of inflammation, dyslipidemia, obesity, and insulin resistance, SAA may play a key role in regulating the contributions of these processes to atherogenesis.Current Atherosclerosis Reports 02/2006; 8(1):62-8. · 2.92 Impact Factor