title: Modulation of cardiometabolic pathways in skin and serum from patients with psoriasis.
abstract: BACKGROUND
  Moderate-to-severe psoriasis is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD); however, the link is poorly understood.
  
  
  METHODS
  Skin and serum from patients with psoriasis were evaluated to understand if there was evidence of dysregulation in a targeted group of inflammatory and lipid genes related to ASCVD. Microarray analyses of expression of targeted ASCVD genes from skin in 89 patients with moderate-to-severe psoriasis from the ACCEPT trial were compared with non-diseased skin from healthy controls (n = 25). Serum (n = 149) was tested at baseline for monocyte chemoattractant protein-1 (MCP-1), macrophage-derived chemokine (MDC), and apolipoprotein-A1 (Apo-A1) comparing to healthy controls (n=162).
  
  
  RESULTS
  An increase in skin gene expression for MCP-1 (7.98-fold) and MDC (6.66-fold) (p < 0.001 each) was observed in lesional versus healthy skin. Significant decreases in liver X receptor-alpha (LXR-α) (-5.94-fold), a protective lipoprotein metabolism gene, and in peroxisome proliferator-activated receptor-alpha (PPAR-α) (-7.58-fold), a protective anti-inflammatory and lipid modulating gene, were observed in lesional versus healthy skin (p < 0.001 each). Serum analyses revealed that MCP-1 (502 vs. 141 pg/mL) and MDC (1240 vs. 409 pg/mL) levels were significantly elevated in psoriasis compared with healthy controls (p < 0.001 each). Dysregulated lipid metabolism was also evident in the serum, as Apo-A1, a protein product related to PPAR-α activation, was significantly decreased in patients with psoriasis compared with healthy controls (25.2 vs. 38.9 mg/dL; p < 0.001).
  
  
  CONCLUSIONS
  Analyses of targeted genes and their products known to be associated with ASCVD revealed dysregulation of inflammatory (MCP-1 and MDC) and lipid metabolism (LXR-α, PPAR-α) genes in psoriasis. These findings provide evidence of a potential shared pathophysiology linking psoriasis to cardiometabolic diseases.
authors: Section of Inflammation and Cardiometabolic Diseases, National Heart Lung and Blood Institute, Bethesda, MD, USA. nehal.mehta@nih.gov.
authors: Nehal N
authors: NN
authors: Mehta
authors: Katherine
authors: K
authors: Li
authors: Philippe
authors: P
authors: Szapary
authors: James
authors: J
authors: Krueger
authors: Carrie
authors: C
authors: Brodmerkel
mesh_terms: D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002633:Chemotaxis; D003710:Demography; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011565:Psoriasis / Q000097:blood* / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000378:metabolism* / Q000473:pathology*
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