HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages
J. Clin. Invest. James Dressman, et al. 111:389 doi:10.1172/JCI16261 [
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Figure 7HIV protease inhibitors induced the formation of atherosclerotic lesions in LDLR null mice. Six-week-old male LDLR null mice on a chow diet were given vehicle control (0.01% ethanol) or the following protease inhibitors in their drinking water: amprenavir (23 or 75 μg/mouse/day), indinavir (25 or 75 μg/mouse/day), or ritonavir (10 or 50 μg/mouse/day). These mice were then used to quantify the surface area of atherosclerotic lesions. To quantify lesions, we first removed the aorta from the arch to the ileal bifurcation and dissected away extraneous tissue. The intimal surfaces were exposed by a longitudinal cut. The aortas were placed under a dissecting microscope equipped with a video camera attachment that captures the image in a computer file. Atherosclerotic lesions on the intimal aortic surface appear as bright white areas compared with the thin and translucent aorta. Areas of intima covered by atherosclerotic lesions were quantified with ImagePro software. This software analyzes differences in contrast to identify areas covered by lesions. Bars represent mean ± SE,
n = 8. *
P < 0.01 compared with vehicle,
#P < 0.01 compared with low dose of the same protease inhibitor.
