Pitavastatin attenuates atherosclerosis by suppressing NF-κB signaling in a high-cholesterol diet plus balloon catheter injury rabbit model.

Atherosclerosis (AS) induced by endothelial cell (EC) dysfunction significantly contributes to the onset and development of cardiovascular disease. Pitavastatin is a member of the lipid-lowering drugs, statins that are widely used in clinics. In the current study, we evaluated the effect of pitavastatin on AS and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in abdominal aortic ECs. We induced AS in rabbits by high-cholesterol diet plus balloon catheter injury. The anti-AS effect of pitavastatin was assessed by measuring the intima-media thickness of the abdominal aorta, minimal lumen area (MLA), minimal lumen diameter (MLD), and other hemodynamic parameters. In addition, we measured the production of total cholesterol (CHOL, high density lipoproteins (HDL), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) in the rabbits. To explore the underlying mechanism of pitavastatin on atherosclerosis, we isolated abdominal aortic ECs and determined the activity of NF-κB signaling. In our model, we found that the affected animals had structural impairments of the heart and arteries: reduced left atrium diameter, right ventricular internal diameter, MLA, and MLD and increased interventricular septal thickness, left ventricular internal diameter, left ventricular posterior wall thickness, right atrium diameter, and intima-media thickness of abdominal aorta. Most of these changes were restored by administration of pitavastatin. Moreover, concentrations of plasma lipids were also attenuated by pitavastatin. At the molecular level, pitavastatin inhibited the expression of NF-κB and Bax and induced the production of IL-1β and Bcl-2. In addition, we demonstrated that the anti-AS effect of pitavastatin depends on restoring normal function of ECs and eliminating dysfunctional ECs by inducing apoptosis.