Lipoprotein apheresis of hypercholesterolemic patients mediates vasoprotective gene expression in human endothelial cells.
OBJECTIVE
Hypercholesterolemia is an important risk factor of cardiovascular diseases. Lipoprotein apheresis is an efficient strategy to reduce the serum low-density lipoprotein (LDL)-cholesterol and lipoprotein(a) levels and cardiovascular complications in patients with severe hypercholesterolemia. The underlying molecular mechanisms are not well-understood. In this study, we analyzed the impact of lipoprotein apheresis on gene expression in human endothelial cells.


METHODS
Human endothelial cells were stimulated with serum of hypercholesterolemic patients before and after lipoprotein apheresis. The expression of endothelial lipoprotein receptors, nitric oxide (NO) synthase and adhesion molecules was quantified by real-time PCR and Western blot.


RESULTS
Lipoprotein apheresis reduced the expression of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in endothelial cells. Low-density lipoprotein (LDL) receptor expression remained unchanged. The mRNA expression of the endothelial nitric oxide synthase (eNOS) was increased with serum of hypercholesterolemic patients after lipoprotein apheresis. In contrast, endothelial expression of vascular cell adhesion molecule 1 (VCAM-1) was reduced in response to serum after lipoprotein apheresis.


CONCLUSIONS
Lipoprotein apheresis reduced the expression of the proatherosclerotic oxLDL receptor LOX-1 and adhesion molecule VCAM-1 and increased the expression of vasoprotective and NO generating eNOS in human endothelial cells in response to serum of hypercholesterolemic patients. These novel molecular mechanisms may account for the antiatherosclerotic and vasoprotective potential of lipoprotein apheresis in patients with hypercholesterolemia.
Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Clinical Center, University Hospital Carl Gustav Carus, Dresden University of Technology, Fetscherstr 74, 01307 Dresden, Germany. Henning.Morawietz@tu-dresden.de
Henning
H
Morawietz
Winfried
W
Goettsch
Melanie
M
Brux
Manja
M
Reimann
Stefan R
SR
Bornstein
Ulrich
U
Julius
Tjalf
T
Ziemssen
D015415:Biomarkers / Q000097:blood; D001781:Blood Component Removal; D015153:Blotting, Western; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D017270:Lipoprotein(a) / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D017270:Lipoprotein(a); D008074:Lipoproteins; C495137:OLR1 protein, human; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E; D014280:Triglycerides; D019010:Vascular Cell Adhesion Molecule-1; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III