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Armstrong AW, Voyles SV, Armstrong EJ et al.A tale of two plaques: convergent mechanisms of T-cell-mediated inflammation in psoriasis and atherosclerosis. Exp Dermatol 20:544-549

Dermatology Clinical Research Unit, Teledermatology Program, Department of Dermatology, University of California, 3301 C St., Suite 1400, Sacramento, Davis, CA 95816, USA.
Experimental Dermatology (Impact Factor: 4.12). 07/2011; 20(7):544-9. DOI: 10.1111/j.1600-0625.2011.01308.x
Source: PubMed

ABSTRACT Psoriasis and atherosclerosis are diseases in which effector T lymphocytes such as Helper T cells type 1 (Th1) and 17 (Th17) play integral roles in disease pathogenesis and progression. Regulatory T cells (Treg) also exert clinically important anti-inflammatory effects that are pathologically altered in psoriasis and atherosclerosis. We review the immunological pathways involving Th1, Th17 and Treg cells that are common to psoriasis and atherosclerosis. These shared pathways provide the basis for mechanisms that may explain the epidemiologic observation that patients with psoriasis have an increased risk of heart disease. Improved understanding of these pathways will guide future experiments and may lead to the development of therapeutics that prevent or treat cardiovascular complications in patients with psoriasis.

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Available from: Ehrin J Armstrong, Nov 28, 2014
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    • "Here we provide evidence of gene dysregulation within the skin and serum in patients with psoriasis, supporting a shared pathophysiology of psoriasis and ASCVD [23]. Future studies may help to address an in vivo link between psoriasis and vascular inflammation using imaging, and by focusing on the effect of psoriasis treatment on CV biomarkers. "
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    ABSTRACT: Moderate-to-severe psoriasis is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD); however, the link is poorly understood. 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) 162 healthy controls was tested at baseline for monocyte chemoattractant protein-1 (MCP-1), macrophage-derived chemokine (MDC), and apolipoprotein-A1 (Apo-A1). 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 psoriasis compared with healthy controls (25.2 vs. 3.89 mg/dL; p < 0.001). 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.
    Journal of Translational Medicine 08/2013; 11(1):194. DOI:10.1186/1479-5876-11-194 · 3.99 Impact Factor
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    • "Caspase-14 Protects against Parakeratosis key importance for the development of psoriatic lesions (reviewed in Armstrong et al., 2011), but no difference was observed in infiltrating leukocyte or T-cell numbers between IMQ-treated WT and caspase-14 À / À skin. The difference in parakeratotic plaque formation in caspase-14-deficient skin was not due solely to the IMQ treatment, because an increase, although less extensive, in epidermal thickness, parakeratosis, and TEWL was also observed upon topical treatment of these mice with vehicle cream, which was not the case in control mice (Figure 6). "
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    ABSTRACT: Caspase-14 is an important protease in the proper formation of a fully functional skin barrier. Newborn mice that are deficient in caspase-14 exhibit increased transepidermal water loss and are highly sensitive to UVB-induced photodamage. Decreased caspase-14 expression and incomplete caspase-14 processing in lesional psoriatic parakeratotic stratum corneum has been reported previously. In this study, we show that caspase-14-deficient skin frequently displays incompletely cornified cells in the transitional zone between the granular and the cornified layers, pointing to a delay in cornification. We also demonstrate that after challenge of epidermal permeability barrier function by repetitive acetone treatment, a higher incidence of large parakeratotic plaques was observed in caspase-14-deficient skin. Furthermore, caspase-14-deficient mice are more prone than control mice to the development of parakeratosis upon induction of psoriasis-like dermatitis by imiquimod treatment. These results show that lack of caspase-14 expression predisposes to the development of parakeratosis and that caspase-14 has an important role in keratinocyte terminal differentiation and the maintenance of normal stratum corneum, especially in conditions causing epidermal hyperproliferation.Journal of Investigative Dermatology advance online publication, 27 September 2012; doi:10.1038/jid.2012.350.
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    ABSTRACT: Psoriasis ist eine genetisch determinierte, chronisch entzündliche Systemerkrankung. Neben charakteristischen Hautmanifestationen treten insbesondere bei mittelschwer bis schwer betroffenen Patienten andere Erkrankungen gehäuft auf. Diese begleitend auftretenden Erkrankungen werden als Komorbiditäten bezeichnet. Metabolische Erkrankungen (wie z. B. Diabetes mellitus, Insulinresistenz, Fettstoffwechselstörungen, meist auf der Grundlage einer Adipositas) und kardiovaskuläre Erkrankungen (wie z. B. arterieller Hypertonus, koronare Herzkrankheit, Myokardinfarkt und Apoplex) sind dabei von besonderer Bedeutung, da sie auch die Mortalität der Patienten beeinflussen können. Aber auch psychiatrische Erkrankungen sind bei Psoriasispatienten häufig und beeinflussen das Therapiemanagement. Der Dermatologe ist in den meisten Fällen der erste Ansprechpartner von Psoriasispatienten und somit die Schlüsselfigur im Therapiemanagement. Er ist dabei auch für die Früherkennung und Therapiesteuerung von Komorbiditäten mitverantwortlich. Die von ihm durchgeführte antipsoriatische Therapie muss mit den vorliegenden Komorbiditäten und deren medikamentösen Therapien abgestimmt werden. Der folgende Beitrag stellt den aktuellen Wissensstand über die psoriatischen Komorbiditäten und ihre Konsequenzen für die Praxis dar.
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