Abstract |
Macrophage scavenger receptors (MSR) promote atherosclerotic lesion formation, and modulation of MSR activity has been shown to influence atherosclerosis. Soluble receptors are effective in inhibiting receptor-mediated functions in various diseases. We have generated a secreted macrophage scavenger receptor (sMSR) that consists of the bovine growth hormone signal sequence and the human MSR A I extracellular domains. sMSR reduces degradation of atherogenic modified low-density lipoproteins and monocyte/macrophage adhesion on endothelial cells in vitro. To test long-term effects of sMSR, atherosclerosis-susceptible LDLR knockout mice were transduced via the tail vein with an adeno-associated virus (AAV) expressing sMSR or control enhanced green fluorescent protein (EGFP), and a Western-type diet was started. Gene transfer caused a temporary elevation in alkaline phosphatase and aspartate amino transferase values without a change in C-reactive protein. sMSR protein was detected in the plasma of the transduced mice by a specific ELISA 6 months after the gene transfer. AAV-mediated sMSR gene transfer reduced atherosclerotic lesion area in the aorta by 21% (P < 0.05) compared to EGFP-transduced control mice. Even though eradication of established disease was not possible, atherosclerotic lesion formation could be modified using AAV-mediated gene transfer of the decoy sMSR.
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Authors | Johanna Jalkanen, Pia Leppänen, Katri Pajusola, Outi Närvänen, Anssi Mähönen, Elisa Vähäkangas, David R Greaves, Hansruedi Büeler, Seppo Ylä-Herttuala |
Journal | Molecular therapy : the journal of the American Society of Gene Therapy
(Mol Ther)
Vol. 8
Issue 6
Pg. 903-10
(Dec 2003)
ISSN: 1525-0016 [Print] United States |
PMID | 14664792
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Lipids
- Receptors, Immunologic
- Receptors, LDL
- Receptors, Scavenger
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Topics |
- Animals
- Aorta
(pathology)
- Arteriosclerosis
(pathology, therapy)
- Dependovirus
- Genetic Therapy
- Genetic Vectors
- Humans
- Lipids
(blood)
- Mice
- Mice, Knockout
- Receptors, Immunologic
(genetics, metabolism)
- Receptors, LDL
(deficiency, genetics)
- Receptors, Scavenger
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