Abstract 502: Arterial Calcification Increases Neointimal Proliferation Following Balloon Injury in Rat Carotid Arteries
Introduction Arterial calcification predicts accelerated restenosis after angioplasty and stenting. We sought to determine how calcification affected neointimal accumulation after balloon injury in the rat carotid.
Hypothesis We propose that transformed SMCs in calcified arteries respond to balloon injury in an accelerated manner through a mechanism involving bone-related factors.
Methods Arterial calcification was induced in male Sprague-Dawley rats weighing 350-400 grams by subcutaneous administration of vitamin D3. Control rats received vehicle. Both groups underwent left carotid balloon injury one week following injection, a time at which significant medial calcification has developed. Arteries were harvested twenty-one days following balloon injury. The degree of neointimal cell proliferation was next assessed by immunohistochemical staining for PCNA. Neointimal hyperplasia was measured by morphometric analysis using standard imaging analysis software.
Results At 3 weeks after carotid balloon injury, mean cellular proliferation as measured by PCNA staining was higher in the intima of calcified than control arteries (63.8 ± 6.0 versus 40.5 ± 9.5 cells/hpf, P=ns). Calcified arteries from Vitamin D3-treated rats, however, had significantly more intimal hyperplasia than control uncalcified arteries (intima-to-media ratio = 1.374 ± 0.071 versus 0.758 ± 0.080, P=0.0021). Intimal and medial areas were also individually larger in calcified than control arteries.
Conclusions Neointimal hyperplasia is accelerated in Vitamin D3-treated rats through a mechanism that partially involves increased SMC proliferation. Calcified vessels may respond differently to balloon angioplasty and this may explain the poorer results of endovascular interventions in patients with arterial calcification. Other factors including accelerated migration and increased matrix synthesis may also be involved. Treatments to inhibit restenosis in calcified arteries may differ from those that work in uncalcified vessels.
- © 2013 by American Heart Association, Inc.