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Induced expression of lectin-like oxidized ldl receptor-1 in vascular smooth muscle cells following Chlamydia pneumoniae infection and its down-regulation by fluvastatin. 2010

D Prochnau, and J Rödel, and Katrin Prager, and Dana Kuersten, and Regine Heller, and E Straube, and H R Figulla
Department of Internal Medicine/Cardiology, Friedrich-Schiller-University of Jena, Jena, Germany. dirk.prochnau@med.uni-jena.de

Microorganisms such as Chlamydia pneumoniae have been shown to infect vascular cells and are believed to contribute to vascular inflammation and atherosclerotic plaque development. Plasma levels of oxidized low density lipoprotein (oxLDL) have received considerable attention as potential predictors of prognosis in atherosclerotic diseases. Lectin-like oxidized LDL receptor-1 (LOX-1) is one of the major receptors for oxidized LDL. It was investigated whether C. pneumoniae infection can stimulate expression of LOX-1 in vascular smooth muscle cells. Expression of LOX-1 in VSMC was measured by RT-PCR and immunoblotting following C. pneumoniae infection. To examine the pharmacological effect of a HMG-CoA reductase inhibitor on LOX-1 expression, cells were co-incubated with fluvastatin immediately after infection. A dose and time dependent expression of LOX-1mRNA and protein was found in C. pneumoniae infected SMC. After heat and UV light treatment of the chlamydial inoculum the level of LOX-1 was reduced to that of mock-infected cultures. Furthermore, treatment of infected cells with fluvastatin decreased LOX-1 expression to baseline levels. The up-regulation of LOX-1 induced by C. pneumoniae could lead to continued lipid accumulation in atherosclerotic lesions. Together with the widespread expression of LOX-1, this might contribute to the epidemiologic link between C. pneumoniae infection and atherosclerosis. The effect of lowering the LOX-1 expression by fluvastatin may provide a pharmacological option of limiting oxLDL uptake via its scavenger receptor.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D008077 Lipoproteins, LDL A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues. Low-Density Lipoprotein,Low-Density Lipoproteins,beta-Lipoprotein,beta-Lipoproteins,LDL(1),LDL(2),LDL-1,LDL-2,LDL1,LDL2,Low-Density Lipoprotein 1,Low-Density Lipoprotein 2,LDL Lipoproteins,Lipoprotein, Low-Density,Lipoproteins, Low-Density,Low Density Lipoprotein,Low Density Lipoprotein 1,Low Density Lipoprotein 2,Low Density Lipoproteins,beta Lipoprotein,beta Lipoproteins
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005229 Fatty Acids, Monounsaturated Fatty acids which are unsaturated in only one position. Monounsaturated Fatty Acid,Acid, Monounsaturated Fatty,Acids, Monounsaturated Fatty,Fatty Acid, Monounsaturated,Monounsaturated Fatty Acids
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077340 Fluvastatin An indole-heptanoic acid derivative that inhibits HMG COA REDUCTASE and is used to treat HYPERCHOLESTEROLEMIA. In contrast to other statins, it does not appear to interact with other drugs that inhibit CYP3A4. 7-(3-(4-Fluorophenyl)-1-(1-methylethyl)-1H-indol-2-yl)-3,5-dihydroxy-6-heptenoate,Fluindostatin,Fluvastatin Sodium,Fluvastatin Sodium Salt,Lescol,XU 62-320,XU 62320,XU-62320,XU 62 320,XU62320
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D016993 Chlamydophila pneumoniae A species of CHLAMYDOPHILA that causes acute respiratory infection, especially atypical pneumonia, in humans, horses, and koalas. Chlamydia pneumoniae

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