Abstract
BackgroundModerate-to-severe psoriasis is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD); however, the link is poorly understood.MethodsSkin 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).ResultsAn 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).ConclusionsAnalyses 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.
Highlights
Moderate-to-severe psoriasis is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD); the link is poorly understood
We hypothesized that ASCVD genes related to inflammation in lesional skin from patients with moderate-to-severe psoriasis may lead to systemic manifestation of inflammation by dysregulated expression of the inflammatory and lipoprotein metabolism proteins in the serum
We report that a targeted group of genes related to ASCVD (MCP-1, Macrophage-derived chemokine (MDC), liver X receptor (LXR)-α, and peroxisome proliferatoractivated receptor (PPAR)-α) are dysregulated in the skin of patients with psoriasis
Summary
Moderate-to-severe psoriasis is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD); the link is poorly understood. Inflammatory skin disease that places some patients at increased risk of myocardial infarction [1], stroke [2], cardiovascular (CV) death [3], overall mortality [4], and other major adverse CV events [5]. The cause for this increased CV risk in psoriasis remains unknown, evidence suggests shared inflammatory pathways in psoriasis and atherosclerosis [6]. MDCs and MCP-1 are strongly chemotactic for monocytes, selected genes related to atherosclerotic cardiovascular disease (ASCVD) to evaluate expression of these select genes in the skin and serum from patients with psoriasis. We hypothesized that ASCVD genes related to inflammation in lesional skin from patients with moderate-to-severe psoriasis may lead to systemic manifestation of inflammation by dysregulated expression of the inflammatory and lipoprotein metabolism proteins in the serum
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