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

Prostaglandins Leukot Essent Fatty Acids. 2022 May:180:102428. doi: 10.1016/j.plefa.2022.102428. Epub 2022 Apr 16.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonic Acid
  • Atorvastatin / pharmacology
  • Atorvastatin / therapeutic use
  • Delta-5 Fatty Acid Desaturase
  • Fatty Acid Desaturases / genetics
  • Fatty Acids
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Linoleic Acid
  • Male
  • Psoriasis* / drug therapy

Substances

  • Delta-5 Fatty Acid Desaturase
  • Fatty Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Arachidonic Acid
  • Linoleic Acid
  • Atorvastatin
  • Fatty Acid Desaturases

Associated data

  • ClinicalTrials.gov/NCT03228017