Research Of The Effects Of Leptin On Atherosclerosis

Coronary heart disease is the leading cause of death worldwide. Broad researches have identified different factors that are responsible for the genesis of atherosclerosis (AS).Recently, it has been demonstrated that leptin may play an important role in AS. Serum leptin is higher in obese persons than in non-obese subjects. Bodary PF et al found that leptin can promote platelet aggregation and arterial thrombosis after vascular injury. Beltowski et al have demonstrated that leptin can inhibit the activity of anti-oxidative enzyme PON1. All these researches, thus, suggest that leptin may play some role in the process of atherosclerosis.Leptin, a poly-peptide hormone with 167 ammo acid, is mainly secreted by fat cells. It is encoded by fat gene. Leptin not only participates in the glucose, fat metabolism and the regulation of body weight, but also contributes to increase in blood pressure and carcinogenesis. Moreover, leptin regulates the production of several pro- and anti-inflammatory cytokines from immune cells. It is also reported that leptin is independently associated with serum C-reactive protein (CRP) level, increases oxidative stress in endothelial cells and decreases arterial distensibility. These results indicate that leptin can probably play an important role in the initiation and progression of atherosclerosis.The aim of present study is to explore the relationship between serum leptin concentration and the angiographic characteristics of coronary atherosclerosis, and to investigate the effects of leptin on the migration and proliferation of vascular smooth muscle cells in vitro, which explicit the function of leptin in the atherosclerosis.This study comprises two parts which are summarized below:Part1 The Relationship between Serum Leptin Concentration and Angiographic Characteristics of Coronary Atherosclerosis Aim To explore the relationship between serum leptin concentration and angiographic characteristic of coronary atherosclerosis. Methods 101 CHD (coronary heart disease) patients who underwent coronary angiography and 96 healthy control subjects were recruited in this study .The angiographic characteristic of coronary artery atherosclerosis was defined with the method of modified Gensini score. The serum leptin concentration of the case group and the healthy control group were measured by radioimmunoassay. Results The serum leptin concentration in the case group was significantly higher than those in the control group(P<0.01). With the development of atherosclerosis, the leptin concentration was increased. There were significant difference between Gensini score 11 and 5(12.90±0.92 vs.8.44±0.57ng/ml,P<0.05).Conclusions The leptin concentration of the case group was significantly higher than those of the control group, and was higher with the severity of atherosclerosis.PartII The Effects of Leptin on the Migration and Proliferation of Vascular Smooth Muscle CellAim To investigate the effects of Leptin on the migration and proliferation in vascular smooth muscle cell in vitro. Methods The smooth muscle cells at passage of 4-6 were incubated with Leptin in different concentrations (0, 20, 40, 80, 100, 200ng/mL) for 24 hours, then modified Boyden's experiment was used to measure the effect of leptin on migration; MTT was used to measure the dosage-effect curve of leptin on the growth of VSMC; and FCM was used to measured the effect of leptin on the cell cyclin. Results The growth of VSMC was promoted with the concentration of Leptin, and reached the maxim at 100ng/mL; so did the effect of leptin on the proliferation index of VSMC. Leptin can promote the migration of VSMC, and the number of migrated cell was promoted with the increase of leptin concentration. Conclusion Leptin can promote the migration and proliferation of vascular smooth muscle cell in vitro, which explicit the effects of leptin in the atherosclerosis.