Abstract 10563: Deficiency of the Long Pentraxin PTX3 Deteriorates Neointimal Hyperplasia After Vascular Injury
Background: Inflammatory response plays an important role in neointimal hyperplasia after vascular injury. Pentraxin 3 (PTX3) is a novel marker for primary local activation of innate immunity and inflammatory responses. While PTX3 shares similarities with classic short pentraxins such as C-reactive protein, it has an unrelated long domain and differs in gene organization, cellular source, and ligands recognized. Although some clinical and experimental evidence suggests that PTX3 is associated with atherosclerosis, relationship between PTX3 and vascular remodeling remains determined. We investigated the effect of PTX3 on the neointimal hyperplasia after 2 different vascular injuries.
Methods and Results: PTX3 systemic knockout (PTX3-KO) mice and wild type littermate (WT) mice were subjected to tube cuff-mediated perivascular and wire-mediated endovascular injuries. At 4 weeks after cuff and wire-mediated injuries, the area of neointimal hyperplasia (NI) and media (M) of femoral arteries were evaluated. PTX3-KO mice showed higher NI/M ratio compared with WT mice after both cuff and wire injuries (1.1 ± 0.3 vs. 0.6 ± 0.2, P < 0.05; 2.1 ± 0.4 vs. 1.2 ± 0.2, P < 0.05; respectively). PTX3-KO mice demonstrated a greater increase in injury-mediated expression of tumor necrosis factor α, interleukin 1β, and monocyte chemoattractant protein 1 in the vascular wall compared with WT mice. Mac-3 positive macrophage accumulation in vessel wall was significantly higher in PTX3-KO mice than in WT mice. Moreover, recombinant PTX3 significantly inhibited proliferation and migration of rat vascular smooth muscle cells induced by tumor necrosis factor α.
Conclusion: Deficiency of PTX3 deteriorated neointimal hyperplasia after vascular injury through production of inflammatory cytokines, macrophage accumulation, and proliferation and migration of vascular smooth muscle cells.
- © 2011 by American Heart Association, Inc.