Strain-dependent vascular remodeling: the "Glagov phenomenon" is genetically determined.

Abstract

Atherosclerosis of the carotid artery, called intima-media thickening (IMT), is a form of vascular remodeling that is an important predictor for cardiovascular events and has a strong genetic component. Recently, we established a mouse model of vascular remodeling based on partial ligation of the carotid, which is relevant to the "Glagov phenomenon." We hypothesized that there would be genetically determined differences in outward remodeling and IMT induced by carotid flow alterations. We compared vascular remodeling among 5 inbred strains of mice. Despite similar changes in flow among the strains in the left carotid artery (LCA), we observed dramatic differences in remodeling of the partially ligated LCA relative to control. The smallest IMT volume (26+/-3 microm3) was found in C3H/HeJ mice, and the largest were in SJL/J (59+/-10 microm3) and FVB/NJ (81+/-6 microm3). Shear stress did not differ after ligation among strains. Lumen area decreased only when stenosis was > or =55%. IMT correlated significantly with outward remodeling among inbred strains (except C3H). There were significant strain-dependent differences in remodeling index (measured as vessel area/IMT), which suggest fundamental alterations in sensing or transducing hemodynamic signals among strains. Among hemodynamic factors, low shear stress and high heart rate were predictive for IMT. Specifically, heart rate (bpm: C3H, 592+/-6; SJL, 649+/-6; FVB, 683+/-7) but not systolic blood pressure (mm Hg: C3H, 116+/-2; SJL, 119+/-1; FVB, 136+/-1) was predictive. The present study indicates that performing a genetic cross of these strains and total genome scan should identify genes that mediate vascular remodeling.