Identification of genes induced by oxidized phospholipids in human aortic endothelial cells.
Oxidized-L-alpha-1-Palmitoyl-2-Arachidonoyl-sn-glycero-3-Phosphorylcholine (Ox-PAPC), a component of mildly oxidized/minimally modified low-density lipoprotein (MM-LDL), accounts for many of the biological activities of MM-LDL. Having hypothesized that Ox-PAPC initiates gene expression changes in endothelial cells that result in enhanced endothelial/monocyte interactions and the subsequent development of atherosclerotic lesions, we used the suppression subtractive hybridization (SSH) procedure to compare mRNA isolated from PAPC-treated human aortic endothelial cells (HAEC) with mRNA isolated from Ox-PAPC-treated cells. Genes induced by Ox-PAPC but not by PAPC in HAEC included genes involved in signal transduction, extracellular matrix, growth factors, chemokines and several genes with unknown functions. The observed pattern of gene induction suggests that Ox-PAPC may play multiple roles in angiogenesis, atherosclerosis, and inflammation and wound healing.
Reddy
Srinivasa T
ST
Atherosclerosis Research Unit, Department of Medicine, Department of Molecular and Medical Pharmacology, University of California Los Angeles, 650 Charles E. Young Drive South, A8-131 CHS, Los Angeles, CA 90095, USA. sreddy@mednet.ucla.edu
Grijalva
Victor
V
Ng
Carey
C
Hassan
Khaled
K
Hama
Susan
S
Mottahedeh
Rachel
R
Wadleigh
David J
DJ
Navab
Mohamad
M
Fogelman
Alan M
AM
D001013:Aorta, Thoracic / Q000166:cytology* / Q000187:drug effects; D015152:Blotting, Northern; D018925:Chemokines / Q000494:pharmacology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008077:Lipoproteins, LDL / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D009693:Nucleic Acid Hybridization; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000494:pharmacology*; D010743:Phospholipids / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation
D018925:Chemokines; D018076:DNA, Complementary; D006133:Growth Substances; D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; D010743:Phospholipids; D012333:RNA, Messenger; C472349:oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine