High density lipoproteins downregulate basic fibroblast growth factor production and release in minimally oxidated-LDL treated smooth muscle cells.
Increase in plasma low density lipoprotein (LDL) levels and/or decrease in high density lipoprotein (HDL) levels are major risk factors for the development of atherosclerosis. An oxidative modification of LDL represents a key process in atherogenesis. It is well known that the LDL/HDL ratio is more important than the individual LDL and HDL levels to predict atherosclerosis. The purpose of our study was to investigate the effects of mildly oxidized LDL (minimally modified LDL: MM-LDL) and HDL, administrated alone or in combination, on the production and release of basic fibroblast growth factor (bFGF) by bovine aortic smooth muscle cells (SMCs) in culture. MM-LDL and HDL have opposite effects on aortic SMCs: MM-LDL increases both bFGF production and release and SMC proliferation, while HDL decreases both bFGF production and release and SMC proliferation. The effects of either MM-LDL or HDL on SMCs are mediated through a Gi-protein-coupled receptor. The simultaneous treatment of SMCs with MM-LDL and HDL (MM-LDL/HDL ratio=4.0) produced the inhibition of MM-LDL effects. Our data suggest that the protective role of HDL could also be exerted through the inhibition of the pro-atherosclerotic effects of MM-LDL on SMCs.
Cucina
Alessandra
A
Department of Surgery "Pietro Valdoni", University of Rome "La Sapienza", Via A. Scarpa, 14, 00161 Rome, Italy. alessandra.cucina@uniromal.it
Scavo
Maria-Principia
MP
Muzzioli
Luca
L
Coluccia
Pierpaolo
P
Ceccarini
Simone
S
Fuso
Andrea
A
Cavallaro
Antonino
A
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D015536:Down-Regulation / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*
D017077:Culture Media, Conditioned; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D016222:Fibroblast Growth Factor 2