An approach to understand the interaction of lipoproteins and vascular endothelial cells

(1)氧化低密度脂蛋白（ox-LDL）中的溶血磷脂酰胆碱（LPC）抑制内皮细胞EDRF/NO的合成。LPC和ox-LDL抑制细胞内信号转导，该信号转导将受体刺激与内皮细胞中第二信使的生物合成联系起来，导致内皮细胞在激活NO合酶所必需的适当细胞内钙信号的产生方面的缺陷。HDL通过清除ox-LDL中的LPC来逆转ox-LDL诱导的内皮依赖性舒张功能的损害。（2）内皮一氧化氮合酶（NOS）的调节在NADPH、FAD和BH_4作为辅助因子存在的情况下，内皮NOS主要受Ca^<2+>/钙调素的调节。PC、LPC和磷脂酰乙醇胺可使NOS活性增强约3倍。观察BAEC中NOS mRNA的表达。LPC或ox-LDL可促进NOS mRNA表达，IFN-α/β可促进NOS mRNA表达，TNF-α则抑制NOS mRNA表达。(3)血管平滑肌细胞诱导型一氧化氮合酶mRNA表达的调控。干扰素γ、TNF α和白细胞介素1 β均显著增加iNOS的mRNA和蛋白水平，与亚硝酸盐的产生平行。TGF-β显著抑制了由这些细胞因子引起的蛋白质水平的增加。

(1) Effect of lipoproteins and lysolipids on endothelium-dependent relaxationWe have demonstrated that lysophosphatidylcholine (LPC) in oxidized low density lipoprotein (ox-LDL) inhibits the synthesis of EDRF/NO in endothelial cells. LPC and ox-LDL inhibit the intracellular signal transduction which links the receptor stimulation to biosynthesis of the second massenger in endothelial cells, leading to an endothelial defect in the generation at appropriate intracellular calcium signals nesessary for activation of NO synthase. HDL reverses the ox-LDL-induced impairment of endothelium-dependent relaxation by removing LPC from ox-LDL(2) Regulation of endothelial NO synthase (NOS)We have purified endothelial NOS from cultured bovine aortic endothelial cells (BAECs). Endothelial NOS was mainly regulated Ca^<2+>/calmodulin in the presence of NADPH,FAD and BH_4 as cofactors. NOS activity was enhanced approximately up to three fold by PC, LPC and phosphatidylethanolamice. NOS mRNA expression was investigated in BAECs. LPC or ox-LDL enhanced NOS mRNA expression.Interferon alpha/beta increased NOS mRNA expression, but TNF-alpha inhibited it.(3) Regulation of inducible NOS (iNOS) mRNA expression in vascular smooth muscle cells. interferon gamma, TNF alpha and interleukin-1beta each markedly increased mRNA and protein levels of iNOS in parallel with the production of nitrite. TGF-beta significantly inhibited the increase in protein levels caused by these cytokines.