Strain-dependent vascular remodeling phenotypes in inbred mice

We have recently established a mouse model of arterial remodeling in which flow in the left common carotid artery of FVB mice was interrupted by ligat ion of the vessel near the carotid bifurcation, resulting in a dramatic red uction of the lumen as a consequence of a reduction in vessel diameter and intimal lesion formation. In the present study we applied this model to var ious inbred strains of mice. Wide variations in the remodeling response wit h regard to reduction in vessel diameter, intimal lesion formation, lumen a rea, and medial hypertrophy were found. On carotid artery ligation SJL/J mi ce revealed the most extensive inward remodeling leading to an approximate 78% decrease in lumen area while lumen narrowing in FVB/NJ mice was largely due to extensive neointima formation as a result of smooth muscle cell (SM C) proliferation. Significant positive remodeling in the contralateral righ t carotid artery with a >20% increase in lumen area was observed in SM/J an d A/J mice. An in vitro comparison of growth properties of SMC isolated fro m FVB/NJ mice and a strain that exhibited very little SMC proliferation (C3 H/HeJ) demonstrated accelerated growth of SMC from FVB/NJ following serum s timulation. In vivo, SMC proliferation in the FVB/NJ strain was preceded by a 37% loss of medial SMC occurring within the 2 days after ligation, howev er, cell death was not detectable in C3H/HeJ mice. These findings suggest t hat the mechanisms leading to lumen narrowing in the vascular remodeling pr ocess are genetically controlled.