Mechanisms Of Oxidized Low-density Lipoprotein In The Early Stage Of Atherosclerosis Formation

Atherosclerosis (AS) is responsible for many cardiovascular diseases including coronary heart disease, stroke, and others. Oxidized low-density lipoprotein (Ox-LDL) has long been regarded as the primary villain initiating atherogenesis by inducing the transfer of monocyte-derived macrophages into foam cells. This further propagates the inflammatory process and starts the atherogenic process which involves many cell types. The integrity and adhesion properties of endothelium are vital for atherogenesis in that monocytes and other leukocytes in blood have to first attach on endothelium and then infiltrate into the sub-endothelial space. The dysfunction of endothelium in integrity or adhesion properties will promote the atherogenetic process.Recently, it was found that Ox-LDL not only exists in atherosclerotic plaques but also in plasma. The concentration of circulating Ox-LDL is relatively low in blood of children, but increases gradually with aging and even dramatically during the course of a disease (e.g. atherosclerosis). It has been found that high concentration of Ox-LDL has a negative effect during the middle or late stage of atherosclerosis by destroying the integrity of endothelium and increasing the adhesion property of endothelial cells. Then, a question will arise whether low concentration of Ox-LDL has similar effects on endothelium or endothelial cells? The purpose of this study is to answer this question.In this study, cell death and cell spreading of endothelial cells were analyzed to evaluate the effects of Ox-LDL on the integrity of endothelium; on the other hand, production of nitric oxide (NO) and cell-surface adhesion force were assayed to evaluate the adhesion properties of endothelium. Surprisingly, high and low concentrations of Ox-LDL have opposed effects on endothelial cells. High concentration of Ox-LDL induced cell death, inhibited cell spreading and NO production, and promoted the cell-surface adhesive force, in agreement with previous reports; whereas low concentration of Ox-LDL promoted cell proliferation and NO production, but inhibited cell spreading and decrease cell-surface adhesive force of endothelial cells. Interestingly, this results indicate that Ox-LDL probably functions as a double-edged sword:in a low concentration, Ox-LDL functions as a "good" guy to prevent leukocytes from adhering on or infiltrating through endothelium; in a high concentration, it functions as a "bad" guy to enhance the adhesion or infiltration of leukocytes which promotes the process of antherogenesis. The data also implies that the presence of a low concentration of circulating Ox-LDL in human blood may perhaps be a good thing, but it seems that maintaining the status of low concentration is vital. This upsets the conventional opinion. Therefore, our research group will keep on studying this in depth and hope more external research groups join us to verify this hypothesis.