Interaction between mild hypercholesterolemia, HDL-cholesterol levels, and angiotensin II in intimal hyperplasia in mice

Two month old C57BL/6 mice were placed on three different diets: 1) normal diet (NC; 0.025% cholesterol), 2) hypercholesterolemic Western-type diet (HC-W; 0.2% cholesterol), and 3) hypercholesterolemic Paigen-type diet (HC-P; 1.25% cholesterol plus 0.5% cholic acid). At 6 months of age, the animals underwent ligation of the left carotid artery and were randomly assigned to vehicle (PBS, subcutaneous) or angiotensin II (Ang II; 1.4 mg/kg/day, subcutaneous) treatment for 4 weeks. Low density lipoprotein-cholesterol levels were similarly increased in both HC diets (NC, 4 ± 3 mg/dl; HC-W, 123 ± 17 mg/dl; HC-P, 160 ± 14 mg/dl). However, the levels of high density lipoprotein- cholesterol (HDL-C) were reduced only in animals fed the HC-P diet (NC, 82 ± 6 mg/dl; HC-W, 79 ± 7 mg/dl; HC-P, 58 ± 7 mg/dl). In Ang II-treated mice, carotid artery ligation induced intimal smooth muscle cell proliferation to a similar extent in NC- and HP-W-fed animals. However, a significantly larger intimal area developed in ligated vessels from Ang II-treated mice fed the HC-P diet (3.6-fold higher than in Ang II-treated NC mice). Together, these results show the accelerating effect of mild hypercholesterolemia, reduced HDL-C levels, and Ang II on intimal hyperplasia after carotid artery ligation in mice.