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BACKGROUND:Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the LDL receptor (LDLr) in hepatocytes, and its expression in mouse liver has been shown to decrease with fenofibrate treatment.

Objective-To determine if niacin can confer cardiovascular benefit by inhibiting vascular inflammation and improving endothelial function independent of changes in plasma lipid and lipoprotein levels. Methods and Results-New Zealand white rabbits received normal chow or chow supplemented with 0.6% or 1.2%(wt/wt) niacin. This regimen had no effect on plasma cholesterol, triglyceride, or high-density lipoprotein levels. Acute vascular inflammation and endothelial dysfunction were induced in the animals with a periarterial carotid collar. At the 24-hour postcollar implantation, the endothelial expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemotactic protein-1 was markedly decreased in the niacin-supplemented animals compared with controls. Niacin also inhibited intima-media neutrophil recruitment and myeloperoxidase accumulation, enhanced endothelial-dependent vasorelaxation and cyclic guanosine monophosphate production, increased vascular reduced glutathione content, and protected against hypochlorous acid-induced endothelial dysfunction and tumor necrosis factor ␣-induced vascular inflammation. Conclusion-Previous human intervention studies have demonstrated that niacin inhibits coronary artery disease. Thisbenefit is thought to be because of its ability to reduce low-density lipoprotein and plasma triglyceride levels and increase high-density lipoprotein levels. The present study showed that niacin inhibits vascular inflammation and protects against endothelial dysfunction independent of these changes in plasma lipid levels. Key Words: niacin Ⅲ inflammation Ⅲ endothelial dysfunction N iacin (nicotinic acid) has been used for more than 30 years to treat plasma lipid disorders and to prevent atherosclerotic cardiovascular disease. 1 At pharmacological doses, niacin reduces low-density lipoprotein cholesterol, plasma triglyceride, nonesterified fatty acid, and lipoprotein(a) levels. Niacin also increases the concentration of high-density lipoproteins (HDLs). 2 Human intervention studies have indicated that treatment with niacin, either alone or in combination with other lipid-lowering agents, can slow or reverse the progression of atherosclerosis and reduce cardiovascular event rates and total mortality in patients with hypercholesterolemia and established atherosclerotic cardiovascular disease. 2 In combination therapy with statins, niacin reduces cardiovascular events 3 and slows coronary atherosclerosis progression. 4 It also reduces coronary stenosis progression in patients with metabolic syndrome. 5 It has always been assumed that these beneficial effects are the result of the lipid-modifying effects of niacin.However, recent data have indicated that niacin also decreases C-reactive protein levels, 6 improves endothelial dysfunction, 7,8 increases the endothelial and leukocyte oxidation-reduction (redox) state in vitro, 9 inhibits cytokine-induced monocyte adhesion to human endothelial cells, 9,10 improves plaque stability, and reduces thrombosis. 11 It...