Proximal to middle left coronary artery flow velocity ratio, as assessed using color Doppler echocardiography, predicts coronary artery atherosclerosis in mice

Background - We aimed to establish a completely noninvasive technique to assess coronary artery atherosclerosis in living mice using proximal to middle left coronary artery (LCA) velocity ratio as assessed with color Doppler echocardiography (CDE). Methods and Results - Three groups of apolipoprotein E/low-density lipoprotein receptor double-knockout (apoE/LDLr dko) mice 10, 40, and 80 weeks of age and 3 additional age-matched groups of C57BL/6 mice were examined under anesthesia. Coronary flow velocity in proximal (V-prox) and middle part (V-mid) of LCA was measured using CDE. A 40-MHz ultrasound biomicroscope (UBM) was used to visualize lumen and outer vessel diameter in the proximal LCA. Flow velocity in the proximal LCA increased significantly with age and remained constant in the middle part in the apoE/LDLr dko mice, whereas velocities at both the sites remained unchanged in C57 mice. CDE-assessed flow velocity ratio (V-prox/V-mid) increased significantly with age in apoE/LDLr dko mice ( P = 0.0055) and correlated significantly to percentage wall thickness, as assessed by UBM ( P = 0.0044; r = 0.65) and histology ( P = 0.0002; r = 0.78). Wall thickness increased with age in the apoE/LDLr dko mice as measured with UBM ( P = 0.0093; r = 0.49), which was also confirmed with histology ( P < 0.0001; r = 0.73). Conclusions - CDE and UBM are useful noninvasive tools to quantify mouse coronary artery atherosclerosis in vivo.