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: 3.76). 07/2011; 20(7):544-9. DOI: 10.1111/j.1600-0625.2011.01308.x
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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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    • "In addition to PsA, severe psoriasis is reported to associate with cardiovascular complications and obesity. These share with psoriasis inflammatory mechanisms such as alterations in angiogenesis and Th-1-mediated inflammation [5]-[7]. This immune-activation further predisposes psoriatic patients to the development of other chronic autoimmune co-pathologies, such as Crohn's disease, chronic obstructive lung disease, and multiple sclerosis, leading to an aggravation of patient clinical condition and a reduction in quality of life and life expectancy [8]. "
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    ABSTRACT: Purpose: Psoriasis is an immune-mediated dermatosis affecting 2% of the world population. Based on severity, different therapies are indicated: systemic drugs (cyclosporine (CsA) and methotrexate (Mtx)) are administered in severe cases; in patients that do not respond or do not tolerate these molecules, biologic drugs (Etanercept, Infliximab, Adalimumab, and Ustekinumab) are used as well. However, an appropriate management of patients still remains a critical goal still. This retrospective observational study investigated the effectiveness of systemic therapies in the treatment of severe psoriatic patients of the Local Health Authority (LHA) of Treviso, focusing on biologic vs synthetic drugs. Methods: The analysis was performed on the databases of territorial and hospital prescriptions, therapeutic plans, exemption code, blood laboratory tests and hospitalizations. Results: The analysis allowed the identification of a cohort of 871 psoriatic patients. Among them, articular, cardiovascular and immune-mediated complications are frequent comorbidities, sharing with psoriasis a similar genetic predisposition and inflammatory basis. In the LHA of Treviso, 11% of identified psoriatic patients were treated with biologics. Considering blood inflammatory parameters (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), the study revealed that the association of biologic and synthetic therapies (methotrexate) significantly reduces patient inflammatory state (mean CRP value <0.5 mg/100mL; mean ESR value<15mm/hour for men and <20mm/hour for women). Conclusions: The obtained results show clearly that innovative therapies represent a real contribution in the treatment of both psoriasis and its well-known comorbidities. An effective management will therefore require a systemic holistic approach, targeting the psoriatic pathology beyond skin.
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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 · 3.93 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.
    Journal of Investigative Dermatology 09/2012; 133(3). DOI:10.1038/jid.2012.350 · 7.22 Impact Factor
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