Background-The circulating levels of secretory nonpancreatic type II phospholipase A 2 (sPLA 2 ) are increased in various chronic inflammatory diseases and the increase in the levels correlates with the disease severity. sPLA 2 may possibly play a role in atherogenesis and is highly expressed in atherosclerotic arterial walls that are known to have inflammatory features. Thus, this study prospectively examined whether circulating levels of sPLA 2 may have a significant risk and prognostic values in patients with coronary artery disease (CAD). Methods and Results-Plasma levels of sPLA 2 were measured in 142 patients with CAD and in 93 control subjects by a radioimmunoassay. The sPLA 2 levels had a significant and positive relations with serum levels of C-reactive protein, a marker of systemic inflammation, and with the number of the traditional coronary risk factors associated with individuals. Multivariate logistic regression analysis showed that higher levels of sPLA 2 (Ͼ246 ng/dL; 75th percentile of sPLA 2 distribution in controls) were a significant and independent risk factor for the presence of CAD. In multivariate Cox hazard analysis, the higher levels of sPLA 2 were a significant predictor of developing coronary events (ie, coronary revascularization, myocardial infarction, coronary death) during a 2-year follow-up period in patients with CAD independent of other risk factors, including CRP levels, an established inflammatory predictor. Conclusions-The increase in circulating levels of sPLA 2 is a significant risk factor for the presence of CAD and predicts clinical coronary events independent of other risk factors in patients with CAD; these results may reflect possible relation of sPLA 2 levels with inflammatory activity in atherosclerotic arteries. (Circulation. 1999;100:1280-1284.)

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Abstract-Lysophosphatidylcholine (lysoPC), which is generated in oxidized LDL (Ox-LDL) and abundantly exists in atherosclerotic arterial walls, has been shown to alter various endothelial functions and induces several endothelial genes expressed in atherosclerotic arterial walls. Nuclear factor-kappa B (NF-B), a pleiotropic transcription factor, plays an important role in regulation of expression of various genes implicated in atherosclerosis. We have previously reported that lysoPC transferred from Ox-LDL to endothelial surface membrane activates endothelial protein kinase C (PKC), leading to modulated endothelial functions. This study was aimed at determining whether lysoPC could modulate activity of transcription factors in cultured human umbilical vein endothelial cells (HUVECs) by using electrophoretic mobility shift assay. LysoPC was found to increase DNA-binding activity of NF-B in HUVECs within 15 minutes, which peaked at 1 to 2 hours and subsequently declined to the baseline level at 6 hours. Lower concentrations (5 to 15 mol/L) of lysoPC markedly increased NF-B activity, but higher concentration (50 mol/L) of lysoPC inhibited the activity. Phorbol 12-myristate 13-acetate, a potent activator of PKC, also augmented NF-B activity in HUVECs, mimicking the effects of lysoPC; furthermore, calphostin C and chelerythrine chloride, specific PKC inhibitors, and ␣-tocopherol, a clinically potent PKC inhibitor, suppressed the lysoPC-induced NF-B activation. These results indicate that lysoPC regulates NF-B activity in a biphasic manner dependent on its concentrations and incubation time in human endothelial cells and the endothelial PKC activation may in part be involved in the lysoPC-induced NF-B activation. Thus, the time course and the positive and negative biphasic regulatory actions of lysoPC on NF-B activity in endothelial cells might exhibit a unique effect of lysoPC in arterial walls on the different stages of atherosclerosis.(Arterioscler Thromb Vasc Biol. 1998;18:568-576.)

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These results indicate that atherosclerotic arteries may be supersensitive to the constrictor effect of superoxide anion derived from CSE. The decrease in endogenous vascular SOD activity may partly contribute to the increased susceptibility to oxidative stress in atherosclerotic arteries.

The results indicate that tranilast suppresses atherosclerotic development partly through direct inhibition of immunological activation of monocytes/macrophages and T cells in the atheromatous plaque.

The aim of this study was to determine whether apolipoprotein A-1 (apoA-1) may suppress the vasomotor dysregulation by oxidized low-density lipoprotein (ox-LDL), which is known to be an atherogenic lipoprotein. The isolated porcine coronary arterial rings and the cultured endothelial cells from the porcine coronary arteries were exposed to ox-LDL in the presence or absence of complexes of apoA-1 with dimyristoylphosphatidylcholine (DMPC/apoA-1), apoA-1 alone, or DMPC alone. DMPC/apoA-1 but not apoA-1 alone or DMPC alone was found to suppress both impairment of endothelium-dependent arterial relaxation and vasocontraction caused by ox-LDL in the isolated porcine coronary arterial rings suspended in organ chambers. DMPC/apoA-1 absorbed lysophosphatidylcholine (LPC) from ox-LDL and decreased the transfer of LPC from ox-LDL to the surface membrane of the cultured endothelial cells, but apoA-1 alone and DMPC alone had no effect. High-density lipoprotein exerted the protective actions mimicking those observed in DMPC/apoA-1. Thus DMPC/apoA-1 decreased the transfer of LPC from ox-LDL to surface membrane by absorbing LPC, leading to the suppression of ox-LDL-induced dysregulation of endothelium-dependent arterial tone. Therefore, apoA-1 appears to require formation of the complexes with phospholipids to prevent the endothelial dysfunction caused by ox-LDL.