| Atherosclerosis is a common disease and harm to human health, In Europe and United States more than50%of the cause of death is closely related to atherosclerosis.The incidence of Atherosclerosis in China has increased year by year in recent years.It’s great significant to find effective and safe anti-atherosclerosis drugs through new mechanism of action.Endothelial cells dysfunction exists in the development of atherosclerosis,so correcting endothelial cells disorders can be effective against the formation of atherosclerosis.Mature endothelial cells has limited capacity to repair damaged endothelial because of low proliferative potential,so reparing large wounds need stem cells. Recent studies support the theory of endothelial progenitor cells. Usually only a small amount of bone marrow-derived endothelial progenitor cells was released into the blood,however,when myocardial infarction happened, more endothelial progenitor cells was mobilized into circulation, reached the site of injury, adhered to the surface of damaged blood vessels, repaired the damage. Movement, statins, estrogen can promote the number and function of endothelial progenitor cells, the mechanisms of endothelial progenitor cells maintenance endothelial function and structural integrity are reparing endothelial cells and promoting the formation of new blood vessels.In recent years, the study of apolipoproteinA-I anti-atherosclerosis structure and biological characteristics found that the A-type helical structure has a strong Binding capacity of the amphiphilic lipid, apolipoproteinA-I mimetic peptide has similar function.Recent studies mostly concentrated on the mature cells in arterial wall and blood, but not on progenitor cells. According to the inflammation and immune injury hypothesis, the damage of structure and functional integrity of endothelial is the starting point of lesion. Endothelial progenitor cells repairing function is the key to maintain the integrity of endothelium. So we assume that apolipoprotein A1mimetic peptide protects the structure and function of endothelial integrity of the system and ultimately reduces the incidence of atherosclerosis by enhancing EPC repair of injured endothelium.Apolipoprotein A-I (apoA-I) mimetic peptide D-4F has been shown to posses anti-atherogenic properties via sequestration of oxidized phospholipids, induction of remodeling of high density lipoprotein and promotion of cholesterol efflux from macrophage-derived foam cells. However, the impact of D-4F on EPC biology remains elusive.EPCs were isolated from the peripheral venous blood of healthy male volunteers and characterized by Dil-acLDL uptake and UEA binding and flow cytometry. Cell proliferation, migration, adhesion, nitric oxide production and endothelial nitric oxide synthase (eNOS) expression in the absence and presence of D-4F or simvastatin (as a positive control), were assayed.We demonstrated that D-4F significantly enhanced EPC proliferation, migration and adhesion in a dose-dependent manner compared with vehicle. However, all of the favorable effects of D-4F on EPCs were dramatically attenuated by preincubation with NOS inhibitor L-NAME. Further, D-4F also increased nitric oxide production in culture supernatant and the levels of eNOS expression and phosphorylation. The stimulatory effects of D-4F (10μg/ml) on EPC biology were comparable to0.5μM simvastatin.These results suggest that eNOS/NO pathway mediates the functional modulation of EPC biology in response to D-4F treatment and support the notion that the beneficial role of D-4F on EPCs may be one of important components of its anti-atherogenic potential. |
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