Study Of The Correlation Between Insulin-like Growth Factor-1in Serum And The Vascular Endothelial Function In Hypercholesterolemia And The Underlying Mechanisms

Objective:To investigate the relationship between insulin-like growth factor-1(IGF-1) in serum and the vascular endothelial function in patients with hypercholesterolemia and the underlying mechanisms.Methods:1. To exlpore the correlation between insulin-like growth factor1(IGF-1), asymmetric dimethy arginine acid (ADMA) and the vascular endothelial function in patients with hypercholesterolemia, We examined the flow-mediated arterial diastolic function (FMD), the levels of insulin-like growth factor1(IGF-1), asymmetric dimethy arginine acid (ADMA), NO and the activity of nitric oxide synthase (NOS) in serum from25patients with hypercholesterolemia and from healthy controls.2.Endothelial cell injury model was established by incubation the human umbical vein endothelial cells (HUVECs) with Ox-LDL (containing Ox-LDL of100ug/ml) for24hours.For the studies on the effect of IGF-1, cells were treated with IGF-1(containing IGF-1of100ng/ml)30min before Ox-LDL treatment. The levels of ADMA, NOS, NO in cell supernatant, the activity of dimethylarginine dimethylamine hydrolase (DDAH) in cell lysate were measured.(3-gal staining was used to assess the degree of endothelial cell senescence by calculating the senescence rate of cell.Results:1.Compared with control group, the FMD, the levels of IGF-1and NO, the activity of NOS in serum from patients with hypercholesterolemia decreased significantly accompanied with a dramatical increase in ADMA level. The changes in NOS, NO and FMD were positively correlated with IGF-1, while the changes in ADMA was negatively correlated with IGF-1. The changes in NOS,NO and FMD were negatively correlated with ADMA; Multiple linear regression analysis showed that:the changes in IGF-1was independently positively correlated with FMD;the changes in ADMA was independently negatively correlated with FMD.2.Compared with the control group, Ox-LDL treatments significantly decreased the activities of DDAH and NOS, the level of NO concomitantly with an increase ADMA level. Beta-galactosidase staining showed that the senescence rate of cell increased in the Ox-LDL group. The effects of Ox-LDL on HUVECs were significantly attenuated in the presence of IGF-1.Conclusion:1.The decrease in IGF-1in peripheral blood may contribute to vascular endothelial dysfunction in patients with hypercholeste-rolemia;2. IGF-1is able to protect HUVECs against Ox-LDL-induced senescence, which is likely involved in regulation of DDAH/ADMA pathway.