Effects of C-reactive protein on atherogenic mediators and adrenomedullin in human coronary artery endothelial and smooth muscle cells

We examined the effects of recombinant human C-reactive protein (rhCRP) on atherosclerosis-related factors in cultured human coronary artery endothelial and smooth muscle cells (HCAECs and HCASMCs). After removing endotoxin from commercial rhCRP preparations using the appropriate column, the purified, (P)-rhCRP retained the ability to Ca2+-dependently bind to phosphorylcholine, but did not augment the secretion of interleukin-6 and MCP-1 from HCAECs, as non-purified (NP)-rhCRP did. By contrast, P-rhCRP elicited 2- to 3-fold increases in the secretion of both hormones from HCASMCs, though the effect was smaller than that obtained with NP-rhCRP. Production of PAI-1 and endothelin-1 was little affected by either rhCRP preparation in either cell type. In addition, P-rhCRP dose-dependently diminished adrenomedullin release from both cell types, but did not affect adrenomedullin receptor expression or function. Our findings highlight the importance of removing endotoxin from commercial rCRP preparations and show that hCRP elicits atherogenic responses from HCASMCs, but not HCAECs. (C) 2004 Elsevier Inc. All rights reserved.