Abstract 1164: Blocking of Angio-Associated Migratory Cell Protein Inhibits Smooth Muscle Cell Migration and Neointima Formation After Vascular Injury in Apolipoprotein E Knockout Mice
Introduction: Angio-associated migratory cell protein (AAMP) was described to participate in angio- and cancerogenesis and is predominantly expressed in cells with a migratory phenotype. We assessed the hypothesis that AAMP contributes to neointima (NI) formation after vascular injury.
Methods: AAMP contents of smooth muscle cells (SMCs) with different phenotypes were quantified by Western blot. Expression of AAMP and density of SMCs were determined in the atherogenic apolipoprotein E knockout (apoE− /−) mouse model or in the porcine coronary restenosis model by immunohistochemistry and by western blot. Migratory potential of SMCs transiently transfected with AAMP sense expression vectors or treated with anti-recombinant AAMP (anti-rAAMP)-antibody was examined using Boyden chamber assays. ApoE− /− mice were treated with anti-rAAMP antibody, and NI area and SMC density in injured carotid arteries were quantified histopathologically.
Results: SMCs of the migratory phenotype displayed increased AAMP expression (34.9 ± 6.0 intensity/area) compared to the quiescent phenotype (3.8 ± 0.3; P < 0.01). Vascular injury enhanced AAMP expression in murine arteries (88.1 ± 6.0 % of NI area) compared to control (32.2 ± 3.1; P < 0.01) and in porcine arteries (38.4 ± 6.2 intensity/area) compared to control (4.9 ± 1.0; P < 0.01) after one week. The NI of coronary arteries displayed elevated AAMP content one week after injury (40.1 ± 6.2 intensity/area) compared to control (10.2 ± 1.1; P < 0.01). SMCs overexpressing AAMP displayed increased migratory potential (51.9 ± 4.1 cells/area) compared to mock transfected cells (32.5 ± 2.3; P < 0.01), and blocking of AAMP reduced migratory potential of medial SMCs (21.5 ± 4.0) or SMCs of the NI (74.4 ± 11.6) compared to control (49.7 ± 3.8 or 164.5 ± 20.6; P < 0.001). Blocking of AAMP reduced NI area development (42.1 ± 2.8 μm2) and NI SMC density (18.3 ± 4.2 % of NI area) compared to isotype control (78.7 ± 3.1; P < 0.01 and 33.3 ± 5.5; P < 0.01) in injured arteries.
Conclusions: Upregulation of AAMP in migratory and neointimal SMCs, increased migratory potential of SMCs overexpressing AAMP, and reduced SMC migration, SMC density, and NI formation under blockade of AAMP indicate a possible contribution of AAMP to NI formation after vascular injury.