Endothelial Lipase Expressed By Endothelial Cells And Its Effects In Atherosclerosis

Atherosclerosis(AS) is an extremely complicated process, its mainly pathologic basis isvascular endothelial cell dysfunction. After endothelial cells injured, the adhesion moleculesare expressed and attract the monocytes, leukocytes and T lymphocytes adhering to theinjured endothelium. Then the early vascular inflammation was occurred, resulted in lipidoses,smooth muscle cells migration and the foam cells formed. The atherosclerotic plaque wasformed after a series of cascade reaction. So it would be useful for prevention and cure ofatherosclerosis to study and elucidate the mechanism of AS. Endothelial lipase(EL), a newmember of the lipoprotein lipase gene family, expressed lower level at normal state invascular endothelial cell(VEC). However its expression was significantly increased whenendothelium was damaged by a sort of factors that may result in AS. Previous study showedthat EL may be an important factor in the occurrence of AS. But their emphasis was mainlyconcentrated on the lipids metabolism. What is the relationship between EL expression andclinical manifest of coronary artery disease(CAD)? Does EL affect adhesion moleculeexpression, affect the proliferation and migration of VEC and smooth muscle cell (SMC) toparticipate in the occurrence of AS? They are not known.To elucidate these problems, we detected EL expression in the circulating endothelial cell (CEC)and analyzed its relationship to the clinical manifest of CAD. Having used human umbilicalvein endothelial cell(HUVEC), we investigated the effects of EL on the expression ofadhesion molecules, the migration and proliferation of VEC and SMC.Methods:The experiments were conducted in three parts. In the first part, CEC was isolated formpatients who received coronary angiography, and the expression of EL in CECs was detected,and the correlation among EL~+/CECs, clinical manifestation of CAD(AMI, UAP, SAP andcontrol group), LDL/HDL, CECs counts and hsCRP were analyzed.In the second part, the HUVEC was treated with TNF-α(10ng/ml, this dose can cause the over-expression of EL), and the expression of adhesion molecules(ICAM-1/VCAM-1/E-selectin) were detected. With different dose(from 0 to 50ng/ml) of the anti-EL antibodypre-treating the HUVEC, the expression of adhesion molecules were detected.In the third part, effects of over expressed EL on the migration, proliferation andapoptosis of HUVEC and effects of EL on the migration, proliferation of smooth muscle cellwere observed.Results:1. EL is expressed in CEC, and the more dangerous of the patient with CAD, the moreexpression of EL in CECs. Its order goes in AMI＞UAP＞SAP＞control group.2. There was significant difference with EL~+/CECs among groups of CAD(P＜0.05). Butthere was no difference with EL~+/CECs between peripheral and coronary sinus blood.3. There was significant correlation between EL~+/CECs and LDL/HDL, hsCRP.4. In patients with CAD, there was positive correlation between coronary jeopardy scoresand EL~+/CECs, count of CECs, hsCRP. And the coefficient of coronary jeopardy scores withEL~+/CECs was highest (r=0.853). The follow-up investigation showed that EL~+/CECs may bean important indicator to judge prognosis for patient with CAD.5.10ng/ml of TNF-α, which can induce the over expression of EL in HUVEC, increasedexpression of adhesion molecules, and this effect was depressed by anti-EL antibody in adose-dependent manner.6. The ability of migration of EL over-expressed HUVECs was increased, and itsapoptosis ratio was also increased, but its proliferation ability was decreased.7. HUVECs with over-expressed EL could promote the migration and proliferation of SMC.Conclusions:1. EL was expressed in VEC in the patient with CAD. Its expression was positivelycorrelated with the clinical risk. EL~+/CECs may be used as an indicator to judge prognosisfor patients with CAD.2. EL could promote VEC to express the adhesion molecules to cause the localinflammation of endothelium and participate in the occurrence of atheroselerosis.3. EL over-expressed VEC may affect the migration and proliferation of itself and VSMCto participate in the pathology of AS.