Vogt, Felix and Zernecke, Alma and Beckner, Marie and Krott, Nicole and Bosserhoff, Anja-Katrin and Hoffmann, Rainer and Zandvoort, Marc A. M. J. and Jahnke, Thomas and Kelm, Malte and Weber, Christian and Blindt, Ruediger (2008) Blockade of angio-associated migratory cell protein inhibits smooth muscle cell migration and neointima formation in accelerated atherosclerosis. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 52 (4). pp. 302-311. ISSN 0735-1097,
Full text not available from this repository. (Request a copy)Abstract
Objectives The aim of this study was to elucidate the role of angio-associated migratory cell protein ( AAMP) for the migration of vascular smooth muscle cells (SMCs) and for the development of neointimal hyperplasia after vascular injury. Background Although AAMP has been shown to participate in angiogenesis and cancerogenesis and is predominantly expressed in cells with a migratory phenotype, involvement of AAMP during neointima ( NI) formation after arterial injury has not been analyzed previously. Methods The AAMP content in SMCs was examined using 2-photon laser-scanning microscopy and subcellular fractioning. Migratory potential of SMCs transiently transfected with AAMP expression vectors, transfected with small interfering ribonucleic acid ( siRNA), or treated with antirecombinant angio-associated migratory cell protein-antibody (anti-rAAMP-ab) was examined using transwell migration chamber assays. Expression of AAMP was determined in the atherogenic apolipoprotein E knockout (apoE (-/-)) mouse model and in the porcine coronary restenosis model by immunohistochemistry and by Western blot. ApoE(-/-) mice were treated intraperitoneally with anti-rAAMP-ab, and wire- injured carotid arteries were examined. Results Angio-associated migratory cell protein is localized in the membrane of SMCs, and its expression is enhanced in NI-derived SMCs. The AAMP overexpression increases, while both treatment with anti-rAAMP- ab and transfection with siRNA decreases SMC migration. Knockdown of AAMP decreases RhoA activity in the membrane fraction of SMCs. The AAMP expression by SMCs is enhanced in both animal models. Anti-rAAMP- ab reduces neointimal SMC density at 1 week and NI formation at 4 weeks in apoE (-/-) mice without affecting proliferation of SMCs. Conclusions These data reveal an important functional role of AAMP in the migration of SMCs, identifying AAMP as a potential target to limit lesion formation after injury.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROGENITOR CELLS; GENE-EXPRESSION; IMMUNOGLOBULIN; HYPERPLASIA; STENT; AAMP; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Oct 2020 07:52 |
| Last Modified: | 28 Oct 2020 07:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30609 |
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