PMID- 23965158
OWN - NLM
STAT- MEDLINE
DCOM- 20140707
LR  - 20211021
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 11
DP  - 2013 Aug 22
TI  - Modulation of cardiometabolic pathways in skin and serum from patients with 
      psoriasis.
PG  - 194
LID - 10.1186/1479-5876-11-194 [doi]
AB  - 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-alpha) (-5.94-fold), a protective lipoprotein 
      metabolism gene, and in peroxisome proliferator-activated receptor-alpha (PPAR-alpha) 
      (-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-alpha 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-alpha, PPAR-alpha) genes in psoriasis. These findings provide 
      evidence of a potential shared pathophysiology linking psoriasis to 
      cardiometabolic diseases.
FAU - Mehta, Nehal N
AU  - Mehta NN
AD  - Section of Inflammation and Cardiometabolic Diseases, National Heart Lung and 
      Blood Institute, Bethesda, MD, USA. nehal.mehta@nih.gov.
FAU - Li, Katherine
AU  - Li K
FAU - Szapary, Philippe
AU  - Szapary P
FAU - Krueger, James
AU  - Krueger J
FAU - Brodmerkel, Carrie
AU  - Brodmerkel C
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130822
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
SB  - IM
MH  - Atherosclerosis/*blood/genetics/*metabolism
MH  - Case-Control Studies
MH  - Chemotaxis
MH  - Demography
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - Humans
MH  - Inflammation/genetics/pathology
MH  - Lipid Metabolism/genetics
MH  - Male
MH  - *Metabolic Networks and Pathways
MH  - Middle Aged
MH  - Oligonucleotide Array Sequence Analysis
MH  - Psoriasis/*blood/*metabolism/pathology
MH  - Skin/*metabolism/*pathology
PMC - PMC3765699
EDAT- 2013/08/24 06:00
MHDA- 2014/07/08 06:00
PMCR- 2013/08/22
CRDT- 2013/08/23 06:00
PHST- 2013/06/11 00:00 [received]
PHST- 2013/08/17 00:00 [accepted]
PHST- 2013/08/23 06:00 [entrez]
PHST- 2013/08/24 06:00 [pubmed]
PHST- 2014/07/08 06:00 [medline]
PHST- 2013/08/22 00:00 [pmc-release]
AID - 1479-5876-11-194 [pii]
AID - 10.1186/1479-5876-11-194 [doi]
PST - epublish
SO  - J Transl Med. 2013 Aug 22;11:194. doi: 10.1186/1479-5876-11-194.