Fig. 1.

Partial carotid artery ligation (PCAL) induces low and disturbed flow (LDF)-dependent formation of atherosclerotic plaque. A: wild-type (WT) mice were injected with AAV-mPCSK9 and placed on a high-fat diet (HFD). PCAL was performed within 1 wk, introducing LDF within the left carotid and maintaining physiological laminar flow patterns within the contralateral right. Vessels were harvested 3 wk after ligation. B: AAV-mPCSK9 injection and HFD feeding of WT mice induce hyperlipidemia with cholesterol in mg/dl 5-fold higher than mice fed normal chow; mean: 537 (SD 191) vs. 102 mg/dl (SD 33). ****P < 0.0001 by 2-group t-test; n = 6–10 mice/group. C: carotid vessels 3 wk after PCAL showing LDF-mediated atherosclerotic plaque development. Unstained carotid vessels (white scale bar, 1 mm) and cross-sectional histopathology of indicated carotid vessels stained with Oil Red O (black scale bar, 50 µm).