Statin therapy upregulates arachidonic acid status via enhanced endogenous synthesis in patients with plaque psoriasis

Abstract

Circulating fatty acids (FA) may be important in the psoriatic pro-inflammatory phenotype. FADS1 converts linoleic acid (LA) to arachidonic acid (AA), a precursor to potent signaling molecules. HMG-CoA reductase inhibitors (statins) increase FADS1/2 expression in vitro. Psoriasis patients (42 ± 14 years/age, 47% male) were randomized to 40 mg of atorvastatin (n = 20) or nothing (n = 10) for two weeks and plasma FA measured pre and post treatment. After treatment, LDL-C was 44% lower in the statin compared to the no-treatment group. Statins increased FADS1/2 expression, and lowered LA 12% (33% - > 29%, p<0.001) and raised AA 14% (7.7% - > 9.0%, p<0.01) with no change in the no-treatment group. In psoriasis, statins enhance AA and decrease LA, consistent with the action of enhanced FADS expression in vivo. Therapies intended to blunt the effects of AA on platelet aggregation, such as aspirin or omega-3 fatty acids, may require dose adjustment when co-administered with atorvastatin. NCT: NCT03228017.

Keywords: Cardiovascular disease; Fatty acids; Inflammation; Psoriasis; Statins.

Conflict of interest statement

Conflicts of Interest

The other authors report no conflicts.

Copyright © 2022. Published by Elsevier Ltd.

Figures

Fig. 1.

Relationship between change in low density lipoprotein (LDL) cholesterol, fatty acid composition and FADS transcript expression. (A) Relationship between percent change in LDL and change in arachidonic acid (AA) and linoleic acid (LA) composition (assessed using Pearson’s correlation coefficient). (B) Fatty acid desaturase (FADS) 1 and 2 whole blood transcript expression at baseline and 2 week follow-up after 40 mg of atorvastatin or no-treatment. FADS expression assessed via whole blood paxgene RNA sequencing with transcripts expressed as normalized count values (NCV). Paired t-tests, *