RGD Reference Report - Adeno-associated virus-mediated gene transfer of a secreted decoy human macrophage scavenger receptor reduces atherosclerotic lesion formation in LDL receptor knockout mice.

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Adeno-associated virus-mediated gene transfer of a secreted decoy human macrophage scavenger receptor reduces atherosclerotic lesion formation in LDL receptor knockout mice.
Authors:	Jalkanen, J Leppanen, P Pajusola, K Narvanen, O Mahonen, A Vahakangas, E Greaves, DR Bueler, H Yla-Herttuala, S
Citation:	Jalkanen J, etal., Mol Ther. 2003 Dec;8(6):903-10.
RGD ID:	2306130
Pubmed:	PMID:14664792 (View Abstract at PubMed)
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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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
MSR1	Human	arteriosclerosis		IMP			RGD
Msr1	Mouse	arteriosclerosis		ISO	MSR1 (Homo sapiens)		RGD
Msr1	Rat	arteriosclerosis		ISO	MSR1 (Homo sapiens)		RGD

Objects Annotated

Genes (Rattus norvegicus)

Msr1 (macrophage scavenger receptor 1)

Genes (Mus musculus)

Msr1 (macrophage scavenger receptor 1)

Genes (Homo sapiens)

MSR1 (macrophage scavenger receptor 1)

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Adeno-associated virus-mediated gene transfer of a secreted decoy human macrophage scavenger receptor reduces atherosclerotic lesion formation in LDL receptor knockout mice.