Author + information
- R. Preston Mason,
- Samuel C.R. Sherratt and
- Robert F. Jacob
Background: Atorvastatin has been shown to reduce cardiovascular events in diabetic patients of diverse ethnicity through cholesterol-lowering as well as cholesterol-independent pathways. The pleiotropic benefits associated with atorvastatin may be related to the reduced oxidation of apoB-containing particles that contribute to atherogenesis. To address this question, we tested the effects of atorvastatin o-hydroxyl active metabolite (ATM) and other statins (rosuvastatin, simvastatin, pravastatin) on lipid oxidation in apoB-containing particles of different sizes, including small dense LDL (sdLDL), LDL, and very large LDL (VLDL), exposed in vitro to hyperglycemic conditions.
Methods: Lipoprotein fractions were isolated from plasma collected from donors of different ethnic backgrounds, preincubated with various statins, and subjected to copper-initiated oxidation. Changes in lipid oxidation were monitored by the colorimetric detection of malondialdehyde (MDA).
Results: Under high-glucose conditions, sdLDL oxidation increased 71% (p=0.0002) as compared to vehicle-treated controls (MDA levels of 15.4 ± 0.74 µM versus 9.03 ± 0.28 µM, respectively). ATM inhibited lipoprotein oxidation in a potent and dose-dependent manner with an IC50 of 3.0 µM, 4.0 µM and 5.0 µM in sdLDL, LDL, and VLDL, respectively. By contrast, none of the other statins significantly inhibited lipoprotein oxidation as compared to vehicle-treated controls. The antioxidant effects of ATM were observed in lipoproteins obtained from both Asian and Caucasian subjects.
Conclusions: These data indicate that atorvastatin has unique antioxidant effects as compared to other statins in various apoB-containing lipoprotein particles under hyperglycemic conditions. This is attributed to the distinct lipophilic and electron stabilization properties of atorvastatin hydroxyl metabolite due, in part, to its phenoxy chemical moiety. The antioxidant benefits of atorvastatin in various atherogenic apoB-lipoprotein particles may be of particular interest in the medical management of type 2 diabetes.
Moderated Poster Contributions
Vascular Medicine Moderated Poster Theater, Poster Hall, Hall C
Saturday, March 18, 2017, 12:45 p.m.-12:55 p.m.
Session Title: Uncovering the Intricacies of Vascular Function
Abstract Category: 38. Vascular Medicine: Basic
Presentation Number: 1228M-05
- 2017 American College of Cardiology Foundation