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HMG‐CoA Reductase Inhibitors Do Not Ameliorate Progressive Atherogenic Changes In Human Macrophages Treated With Systemic Lupus Erythematosus Patient Plasma: Implications For Statin Use and Novel Insight Into Systemic Lupus Erythematosus
Author(s) -
Arain Hirra A.,
Petri Michelle,
Kasselman Lora J.,
Renna Heather A.,
Zhen Juan,
De Leon Joshua,
Carsons Steven E.,
Reiss Allison B.,
Dores Michael R.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.813.5
Subject(s) - abcg1 , atorvastatin , abca1 , medicine , statin , immunology , foam cell , inflammation , systemic lupus erythematosus , cholesterol , pharmacology , disease , lipoprotein , chemistry , biochemistry , transporter , gene
Systematic lupus erythematosus (SLE) is an inflammatory autoimmune disease that predisposes patients to develop atherosclerotic cardiovascular disease (CVD). Like the disease itself, the etiology by which SLE promotes CVD remains largely unknown. The most prevalent treatment for CVD is HMG‐CoA reductase inhibitors, used due to its lipid lowering and inflammation attenuating properties. Due to the need for CVD treatment in SLE, the Lupus Atherosclerosis Prevention Study (LAPS) investigated the efficacy of the HMG‐CoA reductase inhibitor atorvastatin in lowering plaque progression in SLE patients and revealed that statins had no effect on atherosclerotic progression. From these findings, we investigated the impact of the HMG‐CoA reductase inhibitor atorvastatin on the reverse cholesterol transport profile in a subset of human macrophages using plasma from SLE subjects in the LAPS trial. These experiments probe how statins may modulate conversion to the foam cell phenotype induced by the autoimmune SLE environment. Previously, we demonstrated that SLE promotes pro‐atherogenic changes in macrophages by decreasing the amount ATP‐binding transporters (ABCA1 and ABCG1) available. ABCA1/ABCG1 are important for transporting cholesterol out of the cell by packaging into nascent high‐density lipoproteins. Here, we demonstrate that statin treatment was not able to attenuate the pro‐atherogenic effects by not reducing the foam cell phenotype produced from the SLE plasma using differentiated macrophages from a human leukemia cell line. Further, our data reveal that the SLE autoimmune environment promotes a progressive atherogenic change in macrophages over time by increasingly suppressing the amount of ABCA1 and ABCG1 transporters while increasing the amount of low‐density lipoprotein receptor (LDLR), the receptor responsible for low‐density lipoprotein uptake. Liver X receptor‐α (LXR‐ α) and peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), two nuclear receptors responsible for up regulating expression of reverse cholesterol transporters, revealed no change in expression in the presence of statins, indicating a possible post‐transcriptional regulation of the ABC transporters by the lupus environment over time. These findings demonstrate that SLE induces progressive atherogenic changes that could not be rescued by HMG‐CoA reductase inhibitors. Support or Funding Information This research was supported by the Elizabeth Daniell Research Foundation. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .