Effects of Native and Myeloperoxidase-Modified Apolipoprotein A-I on Reverse Cholesterol Transport and Atherosclerosis in Mice

• DOI: 10.1161/atvbaha.113.303044
• Publication Date: 2014-01-10T05:32:10Z
• Authors: Bernd Hewing; Saj Parathath; Tessa Barrett; Wing Ki Kellie Chung; Yaritzy M. Astudillo; Tadateru Hamada; Bhama Ramkhelawon; Thomas C. Tallant; Mohamed Shaif S. ...; Joseph A. DiDonato; Ying Huang; Jennifer Buffa; Stela Z. Berisha; Jonathan D. Smith; Stanley L. Hazen; Edward A. Fisher
• Keywords: Reverse cholesterol transport; Scavenger Receptor; Apolipoprotein E; High-density lipoprotein

Preclinical and clinical studies have shown beneficial effects of infusions apolipoprotein A-I (ApoA-I) on atherosclerosis. ApoA-I is also a target for myeloperoxidase-mediated oxidation, leading in vitro to loss its ability promote ATP-binding cassette transporter A1-dependent macrophage cholesterol efflux. Therefore, we hypothesized that oxidation would impair promotion reverse transport vivo the atherosclerotic plaques.ApoA-I(-/-) or E-deficient mice were subcutaneously injected with native human ApoA-I, oxidized (myeloperoxidase/hydrogen peroxide/chloride treated), carrier. Although early postinjection (8 hours) levels total plasma similar versus primarily resided within high-density lipoprotein fraction, whereas majority was highly cross-linked not particle associated, consistent impaired A1 interaction. In ApoA-I(-/-) mice, significantly vivo. advanced aortic root plaques injections led significant decreases lipid content, number, an increase collagen content; contrast, failed mediate these changes. The decrease plaque macrophages accompanied by induction their chemokine receptor CCR7. Furthermore, only reduction inflammatory M1 anti-inflammatory M2 markers plaques.Myeloperoxidase-mediated renders dysfunctional unable (1) transport, (2) changes composition plaques, (3) pacify status macrophages.