The Study Of Effect Of GDF11 On Foam Cell Formation And Related Molecules Mechanism

Atherosclerosis(AS) is one of the most common cardiovascular diseases, which is usually observed in aeteria coronaria and abdominal aorta. The pathological mechanism of AS is complicated. Oxidated-1ow density lipoprotein(ox LDL), especially those deposited under endangium, plays an important role on the development of AS. Previous studies have proved that the permeability is increased in damaged vascular endothelial cells,which could been through by 1ow density lipoprotein(LDL). Then deposited LDL becomes oxLDL by oxidative modify. In this process, vascular endothelial cells secrete many inflammatory factors and chemotatic factors to recruit monocytes/macrophages in systema circulatorium to engulf oxLDL. Macrophages, which phagocytizing much ox LDL,become the source of foam cells. During the migration and phagocytosis, macrophages also secrete many inflammatory factors and matrix degraded factors, facilitating the development of AS.Growth differentiation factor 11(GDF11), which belongs to superfamily of TGF-?,participates on the development of some tissues or organs, including vertebrae, nerve andpancreatic island. GDF11 also has effect on some diseases, such as type ? thalassemia and dentin renovation. GDF11 in systema circulatorium is decreased with aging in mice and the concentration of GDF11 shows negative correlation with cardiac enlargement. When exogenous GDF11 added by intraperitoneal injection, cardiac enlargement of aged mice is obviously improved. But the effect of GDF11 on AS or monocytes/macrophages has not been reported.In this study, RAW264.7 cells were treated with oxLDL at different concentrations,lipidladen macrophages, mRNA and protein expression of GDF11, inflammatory factors and matrix degraded factors were detected by BODIPY staining, Real-time PCR and Western Blot analysis. The effect of exogenous GDF11 on lipid deposition, inflammatory and matrix degraded factors expression was detected by the same methods. The possible mechanism between GDF11 and foam cell formation was also studied.Results1. High concentration of oxLDL increased the percentage of BODIPY-positive cells,as well as the mRNA expression of IL-1, IL-6 and MMP-9. But the mRNA and protein expression of GDF11 was decreased under stimulation of oxLDL.2. The percentage of BODIPY-positive cells, as well as the m RNA expression of IL-1, IL-6 and MMP-9, were decreased under stimulation of high concentration oxLDL with exogenous GDF11.3. High concentration of oxLDL increased mRNA expression of CD36 and decreased mRNA expression of ABCA1 and ABCG1. Exogenous GDF11 could reverse the expression change of molecules mentioned above.4. High concentration of oxLDL increased m RNA expression of PPAR-?, which could be reversed by exogenous GDF11.Conclusions:1. High concentration of oxLDL could facilitate the development of AS by enhancing the formation of foam cells, as well as the expression of inflammatory factors and matrix degraded factors.2. High concentration of oxLDL could inhibit the expression of GDF11. ExogenousGDF11 could decelerate the development of AS by decreasing the formation of foam cells,as well as the expression of inflammatory factors and matrix degraded factors.3. GDF11 could decrease the expression of molecules related to cholesterol c and increase the expression of molecules related to cholesterol excretion to regulated the formation of foam cells.4. The effect of GDF11 on the expression of molecules related to cholesterol intake/excretion might be regulated by PPAR-?.