Effect Of Trans Fatty Acid On Proliferation And Function Of Human Umbilical Vein Smooth Muscle Cells

Atherosclerosis (AS) was a kind of complicated vascular endothelial disease. Monocyte adhere to the endothelial cells (ECs) and enter into sublayer of intima as well as smooth muscle cells (SMCs) migrate to intima from tunica media followed by the formation of fibroatheroma were the main process of AS. As a independent risk factor of cardiovascular disease, trans fatty acids (TFA) were gained more and more concentrations in recent years. A series of studies has demonstrated the adverse effect of TFA on AS, but most of them focused on the effect of TFA on endothelial cells, the role of SMCs in the progress of AS induced by TFA was not clear. Further more, the researches about the relationship of TFA and AS more concerned with TFA compound, the effect of different saturations TFA on AS was barely detected. However, some researchers found that elaidic acid (9t18:1) and linolelaidic acid (9tl2tl8:2) which widespread exist in Chinese food may induce apoptosis of ECs through caspase pathway and promote the release of inflammatory factors in intima. Therefore, it is imperative for us to investigate the underlying mechanisms of how9t18:1and9tl2t18:2influence on AS by investigation SMCs through FACS、Western-Blot、 Real-time PCR and molecule biological methods.Firstly, this research detected the effect of different concentrations of9t18:1and9t12tl8:2on cell viability, cell cycle distribution and fatty acids composition. Then we investigated the mechanism of TFA induced AS by analyzing genes and proteins related to cell proliferation of SMCs. Finally, we observed the effect of TFA on function of ECs that co-cultured with SMCs. The main results of this study are as follows:1.9t18:1and9tl2tl8:2induced HUVSMCs proliferation at low concentration, especially50μM of9t18:1and20μM of9t12t18:2.(cell viability raised to114.30±0.6%and118.5±0.57%respectively after incubation with TFA for48h compared with control group). But high concentration of TFA (100μM or higher) showed cytotoxicity and induced apoptosis of HUVSMCs.2.9t18:1and9t12t18:2induced decrease of PUFA, especially n-3PUFA, and the composition of TFA in cells was significantly increased.3. The percentage of HUVSMCs in S phase was obviously added after treated by TFA.4. The two different TFAs can both increase CDK2. CyclinE and PCNA mRNA and protein expression, but p21was inhibited.5. TFA can induce ICAM-1, ECAM-1and e-NOS mRNA expression of ECs when it was co-cultured with HUVSMCs by closely contact.