Neointima formed by arterial smooth muscle cells expressing versican variant V3 is resistant to lipid and macrophage accumulation

Merrilees, Mervyn J., Beaumont, Brent W., Braun, Kathleen R., Thomas, Anita C., Kang, Inkyung, Hinek, Aleksander, Passi, Alberto and Wight, Thomas N. (2011) Neointima formed by arterial smooth muscle cells expressing versican variant V3 is resistant to lipid and macrophage accumulation. Arteriosclerosis, Thrombosis, and Vascular Biology, 31 6: 1309-1316. doi:10.1161/ATVBAHA.111.225573


Author Merrilees, Mervyn J.
Beaumont, Brent W.
Braun, Kathleen R.
Thomas, Anita C.
Kang, Inkyung
Hinek, Aleksander
Passi, Alberto
Wight, Thomas N.
Title Neointima formed by arterial smooth muscle cells expressing versican variant V3 is resistant to lipid and macrophage accumulation
Journal name Arteriosclerosis, Thrombosis, and Vascular Biology   Check publisher's open access policy
ISSN 1079-5642
1524-4636
Publication date 2011-06
Sub-type Article (original research)
DOI 10.1161/ATVBAHA.111.225573
Open Access Status
Volume 31
Issue 6
Start page 1309
End page 1316
Total pages 8
Place of publication Philadelphia, United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted abstract
Objective—Extracellular matrix (ECM) of neointima formed following angioplasty contains elevated levels of versican, loosely arranged collagen, and fragmented deposits of elastin, features associated with lipid and macrophage accumulation. ECM with a low versican content, compact structure, and increased elastic fiber content can be achieved by expression of versican variant V3, which lacks chondroitin sulfate glycosaminoglycans. We hypothesized that V3-expressing arterial smooth muscle cells (ASMC) can be used to form a neointima resistant to lipid and macrophage accumulation associated with hypercholesterolemia.

Methods and Results—ASMC transduced with V3 cDNA were seeded into ballooned rabbit carotid arteries, and animals were fed a chow diet for 4 weeks, followed by a cholesterol-enriched diet for 4 weeks, achieving plasma cholesterol levels of 20 to 25 mmol/L. V3 neointimae at 8 weeks were compact, multilayered, and elastin enriched. They were significantly thinner (57%) than control neointimae; contained significantly more elastin (118%), less collagen (22%), and less lipid (76%); and showed significantly reduced macrophage infiltration (85%). Mechanistic studies demonstrated that oxidized low-density lipoprotein stimulated the formation of a monocyte-binding ECM, which was inhibited in the presence of V3 expressing ASMC.

Conclusion—These results demonstrate that expression of V3 in vessel wall creates an elastin-rich neointimal matrix that in the presence of hyperlipidemia is resistant to lipid deposition and macrophage accumulation.
Keyword Lipids
Macrophages
Elastin
Hypercholesterolemia
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Australian Institute for Bioengineering and Nanotechnology Publications
 
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