我们发现正常的HDL提高COX2表达和PGI-2释放的原因除了所含的鞘磷脂S1P外，还有apoA-I。对于糖尿病HDL，我们发现糖尿病HDL具有更显著上调COX2表达和PGI-2释放，而这些功能与apoA-I的修饰无关，而是由于S1P大量汇集造成，我们通过S1P特异性的受体抑制剂等都证明了这推论。在前期青年基金的支持下发表SCI文章13篇（责任作者10篇）。由于S1P代谢中有两个很重要的前体，ceramide和sphingosine。这两个前体却与S1P不同，他们对内皮有破坏作用。我们的研究将集中研究糖尿病HDL中S1P如何增加以及糖尿病后期减少的原因，并且S1P是如何与它的前两个前体形成一种平衡。同时我们将进一步研究在糖尿病状态下，S1P的量的改变是否涉及到与它代谢密切相关的3个合成酶或分解酶的量与活性。我们将结合临床样品，代谢生物质谱技术，糖尿病小鼠模型等进行研究。

With the help of previous funding, we published 8 papers (7 with me as corresponding author). We previously found normal HDL can up regulate COX2, and release PGI-2, which have protective effects to endothelial cells. Not only S1P but also apoA-I has this function. And, we found diabetic HDL has more significant protection effects in inducing COX2 expression and PGI-2 release, which is due to the increased level of S1P level in diabetic HDL, not modification of apoA-I. We also used specific inhibitor of S1P receptor to prove this phenomenon. The precursors of S1P are ceramide and sphingosine, which has negative effects on endothelial cells. We want to study how S1P can be increased in diabetic HDL; how S1P keep the balance of function with ceramide and sphingosine; and the quantity and activity of enzymes related to the level of S1P have been changed in diabetes. We will use different approaches including clinical samples, mass spec. technology, diabetic mouse model, etc. to study S1P and other sphingomyelin-like lipids in diabetic HDL.