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    Pivotal Role of mTOR in Non-Skin Manifestations of Psoriasis
    (2024)
    Ka Joo
    ;
    Claudio Karsulovic
    ;
    Milisa Sore
    ;
    HOJMAN CANO, LIA PAULA  
    <jats:p>Psoriasis is a chronic inflammatory condition affecting 2% of the Western population. It includes diverse manifestations influenced by genetic predisposition, environmental factors, and immune status. The sustained activation of mTOR is a key element in psoriasis pathogenesis, leading to an uncontrolled proliferation of cytokines. Furthermore, mTOR activation has been linked with the transition from psoriasis to non-skin manifestations such as psoriatic arthritis and cardiovascular events. While therapies targeting pro-inflammatory cytokines have shown efficacy, additional pathways may offer therapeutic potential. The PI3K/Akt/mTOR pathway, known for its role in cell growth, proliferation, and metabolism, has emerged as a potential therapeutic target in psoriasis. This review explores the relevance of mTOR in psoriasis pathophysiology, focusing on its involvement in cutaneous and atheromatous plaque proliferation, psoriatic arthritis, and cardiovascular disease. The activation of mTOR promotes keratinocyte and synovial cell proliferation, contributing to plaque formation and joint inflammation. Moreover, mTOR activation may exacerbate the cardiovascular risk by promoting pro-inflammatory cytokine production and dysregulation lipid and glucose metabolism. The inhibition of mTOR has shown promise in preclinical studies, reducing skin inflammation and plaque proliferation. Furthermore, mTOR inhibition may mitigate cardiovascular risk by modulating cholesterol metabolism and attenuating atherosclerosis progression. Understanding the role of mTOR in psoriasis, psoriatic arthritis, and cardiovascular disease provides insight into the potential treatment avenues and sheds light on the complex interplay of the immune and metabolic pathways in these conditions.</jats:p>
    Scopus© Citations 11  7
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    Scopus© Citations 21  1
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    New Markers for Cardiovascular Disease in Psoriatic Patients: Preliminary Study on Monocyte Phenotype, ADAMTS7, and mTOR Activity
    (2023)
    Khanty Loyola
    ;
    Claudio Karsulovic
    ;
    CABRERA MORAGA, RAUL ALEJANDRO  
    ;
    Claudio Perez
    ;
    HOJMAN CANO, LIA PAULA  
    <jats:p>Psoriasis is a skin disease with occasional involvement of non-cutaneous territories. Beyond the usual, cardiovascular events are more frequent in these patients and correlate only partially with disease activity, suggesting the presence of other unknown factors. We selected ten psoriatic patients without treatment in the last year and matched them for age and gender with eleven healthy subjects. Ficoll-extracted mononuclear cells were analyzed with flow cytometry for monocyte surface phenotype markers, intracellular NFκB/inflammasome-dependent interleukins, and chemotaxis receptor CXCR3. Using ELISA, patient serum was evaluated for ADAMTS7 and CXCL10. Inflammatory M1 monocytes showed higher levels of IL-1β and IL-6 in psoriatic patients. M2 monocytes also showed higher levels of intracellular inflammatory cytokines. Nevertheless, IL-6 values were higher compared to other monocytes and IL-1β. The mTORC activation markers ADAMTS7 and S6Rp were higher in psoriatic patients than in healthy controls. In psoriatic patients, serum levels of ADAMTS7 were elevated, and M2 monocytes showed a distinct inflammatory response with higher relative levels of NFκB-dependent IL-6 and less activity of the CXCR3–CXCL10 chemotactic pathway. These data suggest pathways with potential markers for prediction and early detection of cardiovascular risk in psoriatic patients.</jats:p>
      41Scopus© Citations 5
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    Comorbidities in Chilean patients with psoriasis: a Global Healthcare Study on Psoriasis
    (2022)
    Fernando Valenzuela
    ;
    Claudia De La Cruz
    ;
    Cristóbal Lecaros
    ;
    Javier Fernández
    ;
    Gonzalo Hevia
    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Psoriasis is a chronic inflammatory skin disease associated with several important medical comorbidities. There are scant data available on the comorbidities of patients with psoriasis in South America.</jats:p> </jats:sec> <jats:sec> <jats:title>Aim</jats:title> <jats:p>To examine the comorbidity profile of adult patients with psoriasis in Chile and its association with severity of psoriasis.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>This was a multicentre, cross-sectional study involving 16 hospitals and clinics in Chile, which used a 48-item questionnaire to study clinician- and patient-reported outcomes and comorbidities. Inferential analyses were performed by psoriasis severity, using Fisher exact test, Student t-test and multivariable logistic regression.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In total, 598 adult patients with psoriasis were included (51.1% male; mean age 49.2 ± 15.1 years); 48.5% mild and 51.4% moderate to severe; Psoriasis Area and Severity Index 11.6 ± 11.5; body surface area 14.7 ± 18.2%. Plaque psoriasis was the most common phenotype (90.2%), followed by guttate (13.4%). Psoriatic arthritis occurred in 27.3% of patients. Comorbidities were reported in 60.2% of all patients with psoriasis. Frequent concomitant diseases were obesity (25.3%), hypertension (24.3%), Type 2 diabetes mellitus (T2DM) (18.7%), dyslipidaemia (17.4%), metabolic syndrome (16.7%) and depression (14.4%). After adjustment, significant associations were found between moderate to severe psoriasis and obesity, T2DM and nonalcoholic fatty liver disease (NAFLD) compared with mild psoriasis.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>We report a large study of comorbidities, including depression, dyslipidaemia, T2DM and NAFLD, in people with psoriasis in Chile. The prevalence of comorbidities with psoriasis in Chile appears similar to that found in Western countries, and emphasizes the importance of assessing patients with psoriasis for risk factors for and presence of, comorbid disease in a multidisciplinary setting.</jats:p> </jats:sec>
      1Scopus© Citations 11
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    Scopus© Citations 22  1
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    International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis
    (2022)
    Astrid M. van Huizen
    ;
    Stef P. Menting
    ;
    Rolland Gyulai
    ;
    Lars Iversen
    ;
    Gayle E. van der Kraaij
      40Scopus© Citations 19