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psoriasis vascular inflammation

Maroula G Kokotou, Dimitris Limnios, Aikaterini Nikolaou, Anastasia Psarra, George Kokotos
The regulation of the catalytic activity of the various phospholipase A2 enzymes is of high importance because these enzymes are involved in various pathological conditions such as arthritis, cardiovascular diseases, neurological diseases, and cancer. Thus, a great effort has been devoted in developing synthetic inhibitors as new agents to treat inflammatory diseases. Some of them have reached clinical trials. Areas covered: This review article discusses the phospholipase A2 inhibitors presented in patent literature from October 2012 to June 2016, their activities in vitro and in vivo as well as the results of clinical trials using synthetic PLA2 inhibitors...
October 8, 2016: Expert Opinion on Therapeutic Patents
R X Hou, R F Liu, X C Zhao, Y R Jia, P An, Z P Hao, J Q Li, X H Li, G H Yin, K M Zhang
Mesenchymal stem cells (MSCs) have pleiotropic immuno-modulatory effects and pro-angiogenic ability, leading to the presumption that MSCs may be involved in the pathogenesis of many inflammatory or autoimmune disorders, including psoriasis. In a previous study, we reported the specific gene expression profile of dermal MSCs from psoriasis. Inflammation- and angiogenesis-related genes, such as lipopolysaccharide-induced tumor necrosis factor-alpha transcription factor (LITAF), dual-specificity protein phosphatase 1 (DUSP1), vascular endothelial growth factor α (VEGFα), and insulin-like growth factor-binding protein-5 (IGFBP5), are abnormally expressed in psoriatic dermal MSCs...
September 2, 2016: Genetics and Molecular Research: GMR
Özge Uluçkan, Erwin F Wagner
Chronic systemic inflammation (CSI) has recently been identified as a major contributor to common diseases ranging from cancer to metabolic disorders and neurologic alterations. In the last decade, we and others have generated genetically engineered mouse models for inflammatory diseases, which enable studying the molecular mechanisms of CSI. Recently, organ cross-talk induced by CSI under homeostatic and pathological conditions has begun to be appreciated. In this review, we will revisit whole organism physiology in relation to CSI originating from epithelial tissues, such as the skin and gut...
September 21, 2016: FEBS Journal
Desanka Výbohová, Katarína Adamicová, Yvetta Mellová, Gabriela Hešková
Epidermal proliferation, inflammatory changes and microvascular augmentation are prominent features of chronic cutaneous psoriatic lesions. The objective of this study was the investigation of blood and lymphatic microvascular changes in relation to epidermal changes and inflammatory infiltration in dermis. Immunohistochemical analysis with antibodies to CD34, podoplanin, vascular endothelial growth factors - A and C (VEGF-A and C) and morphometric software were used for quantification of the following parameters: blood and lymphatic vessel area (BVA and LVA), VEGF - A and VEGF-C positive area, inflammatory cell infiltration in dermis (CIA) and epidermal area (EA)...
September 16, 2016: Histology and Histopathology
Junfeng Zhang, Yi Lin, Chunlei Li, Xiaomei Zhang, Lin Cheng, Lei Dai, Youcui Wang, Fangfang Wang, Gang Shi, Yiming Li, Qianmei Yang, Xueliang Cui, Yi Liu, Huiling Wang, Shuang Zhang, Yang Yang, Rong Xiang, Jiong Li, Dechao Yu, Yuquan Wei, Hongxin Deng
IL-35 downregulates Th17 cell development and suppresses certain types of autoimmune inflammation such as collagen-induced arthritis and experimental autoimmune uveitis. Psoriasis is thought to be initiated by abnormal interactions between cutaneous keratinocytes and systemic immune cells. However, the role of IL-35 in psoriasis remains unclear. In this study, we assessed IL-35 in three well-known psoriasis models: a human keratinocyte cell line (HaCaT), a keratin 14 (K14)-vascular endothelial growth factor A (VEGF-A)-transgenic (Tg) mouse model, and an imiquimod-induced psoriasis mouse model...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Dilek Biyik Ozkaya, Nahide Onsun, Bugce Topukçu, Ozlem Su, Anil Gulsel Bahalı, Didem Dizman, Aylin Rezvani, Omer Uysal
INTRODUCTION: Psoriasis is a chronic, immune-mediated inflammatory disease predominantly affecting the skin, with a complex aetiology. Recently it has been suggested that the chronic inflammation of psoriasis may cause metabolic and vascular disorders. The relationship between obesity and psoriatic arthritis (PsA) is not clear, and there are insufficient prospective studies addressing this subject. AIM: To investigate the relationship between psoriatic arthritis, severity of psoriasis and obesity in the Turkish population...
June 2016: Postȩpy Dermatologii i Alergologii
Hsien-Yi Chiu, Po-Ching Lo, Weng-Foung Huang, Yi-Wen Tsai, Tsen-Fang Tsai
BACKGROUND: Inflammation of systemic and vascular tissues besides the skin in psoriasis is associated with cardiovascular morbidity and mortality. OBJECTIVE: We sought to investigate whether or not patients with psoriasis have an increased risk of aortic aneurysm (AA). METHODS: This population-based cohort study identified 34,301 patients with psoriasis in the Taiwan National Health Insurance Research Database during 2004 to 2006, who were matched for age and sex with 137,204 control subjects without psoriasis from the Taiwan Longitudinal Health Insurance Database 2000...
October 2016: Journal of the American Academy of Dermatology
S Santilli, D R Kast, I Grozdev, L Cao, R L Feig, J B Golden, S M Debanne, R C Gilkeson, C E Orringer, T S McCormick, N L Ward, K D Cooper, N J Korman
BACKGROUND: Psoriasis is a chronic inflammatory disease of the skin and joints that may also have systemic inflammatory effects, including the development of cardiovascular disease (CVD). Multiple epidemiologic studies have demonstrated increased rates of CVD in psoriasis patients, although a causal link has not been established. A growing body of evidence suggests that sub-clinical systemic inflammation may develop in psoriasis patients, even from a young age. We aimed to evaluate the prevalence of atherosclerosis and identify specific clinical risk factors associated with early vascular inflammation...
2016: Journal of Translational Medicine
Tsion M Aberra, Aditya A Joshi, Joseph B Lerman, Justin A Rodante, Asha K Dahiya, Heather L Teague, Qimin Ng, Joanna I Silverman, Alexander V Sorokin, Taufiq Salahuddin, Benjamin N Lockshin, Mark A Ahlman, Martin P Playford, Marcus Y Chen, Joel M Gelfand, Nehal N Mehta
BACKGROUND AND AIMS: Psoriasis is a chronic inflammatory disorder associated with vascular inflammation, measured by 18-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG PET/CT), and an increased risk of myocardial infarction. Patients with psoriasis are also more likely to suffer from comorbid depression. Whether depression accelerates the development of subclinical atherosclerosis in psoriasis is unknown. METHODS: Patients were selected from within a larger psoriasis cohort...
August 2016: Atherosclerosis
Farrah Ali, Bilal Azhar Khan, Sarwat Sultana
UVB (Ultra-violet B) radiation is one of the major etiological factors in various dermal pathology viz. dermatitis, actinic folliculitis, solar urticaria, psoriasis and cancer among many others. UVB causes toxic manifestation in tissues by inciting inflammatory and tumor promoting events. We have designed this study to assess the anti-inflammatory and anti-tumor promotion effect of Wedelolactone (WDL) a specific IKK inhibitor. Results indicate significant restoration of anti-oxidative enzymes due to WDL treatments...
September 5, 2016: European Journal of Pharmacology
J Muto, N Fujimoto, K Ono, T Kobayashi, K R Chen, S Suzuki, H Wachi, S Tajima
BACKGROUND: Neutrophil elastase plays an important role in skin inflammation induced by neutrophil infiltration. Elafin is an inducible elastase inhibitor expressed by keratinocytes, and is known to be involved in pathogenesis of neutrophilic skin disorders such as psoriasis. METHODS: Immunohistochemical studies of elafin expression in the cases of vasculitis were performed. Induction of elafin expression in cultured vascular cells and its effect on neutrophil migration were studied in vitro...
September 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Louisa Cheung, Rachel M Fisher, Natalia Kuzmina, Dongqing Li, Xi Li, Olivera Werngren, Lennart Blomqvist, Mona Ståhle, Ning Xu Landén
Psoriasis is an immune-mediated inflammatory disease, which is associated with a high risk of developing systemic comorbidities, such as obesity, cardiovascular disease, and diabetes mellitus. However, the mechanistic links between psoriatic skin inflammation and systemic comorbidities remain largely unknown. MicroRNAs (miRNAs) are recently discovered gene regulators that play important roles in psoriasis skin inflammation. In this study we aimed to explore whether the skin inflammation in psoriasis affects miRNA expression of the underlying subcutaneous adipose tissue and whether this may be a link between psoriasis and comorbidities...
March 2016: Journal of Investigative Dermatology
Hisayo Nishida-Fukuda, Ryoichi Araki, Masachika Shudou, Hidenori Okazaki, Yasuko Tomono, Hironao Nakayama, Shinji Fukuda, Tomohisa Sakaue, Yuji Shirakata, Koji Sayama, Koji Hashimoto, Michael Detmar, Shigeki Higashiyama, Satoshi Hirakawa
Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), a type I transmembrane glycoprotein, is known as one of the most specific lymphatic vessel markers in the skin. In this study, we found that the ectodomain of LYVE-1 undergoes proteolytic cleavage, and this process produces soluble LYVE-1. We further identified the cleavage site for ectodomain shedding and generated an uncleavable mutant of LYVE-1. In lymphatic endothelial cells, ectodomain shedding of LYVE-1 was induced by vascular endothelial growth factor (VEGF)-A, an important factor for angiogenesis and lymphangiogenesis under pathological conditions...
May 13, 2016: Journal of Biological Chemistry
Tuba Bozduman, Sibel Ersoy Evans, Sevilay Karahan, Yildiz Hayran, Filiz Akbiyik, Incilay Lay
BACKGROUND: Evidence regarding the vascular endothelial growth factor A (VEGFA) as a potent mediator of angiogenesis and inflammation in psoriasis has revealed variations in this gene as surrogate markers of psoriasis. OBJECTIVE: VEGFA gene polymorphisms (-1540 C/A, -1512 Ins18, -460 T/C, and +405 C/G) in psoriasis susceptibility in Turkish population were investigated. METHODS: A total of 200 age, sex and ethnicity-matched psoriatic and healthy individuals were examined for clinical type, response to therapy, serum VEGFA and its receptor levels, genotypes and haplotypes...
February 2016: Annals of Dermatology
C Bergmann, L Strohbuecker, R Lotfi, A Sucker, I Joosten, H Koenen, A Körber
BACKGROUND: Psoriasis vulgaris (PV) is an autoimmune-related chronic inflammatory disease, which appears mostly in skin, but also affects the vascular and metabolic system. The incidence of PV is 2-3% in the general population and there is still no possibility to cure. Trigger factors have been identified to initiate and maintain inflammation in the skin, which is characterized by Th1-, Th17- and Th22- cells. OBJECTIVE: We hypothesize that the damage-associated molecular pattern (DAMP) molecule high mobility group box 1 (HMGB1) plays a role in the pathogenesis of PV...
March 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
W J Chang, X P Niu, R X Hou, J Q Li, R F Liu, Q Wang, C F Wang, X H Li, G H Yin, K M Zhang
Psoriasis is a common chronic relapsing inflammatory skin disease, in which mesenchymal stem cells (MSCs) have been hypothesized to play an important role in abnormal localized inflammation and vascular proliferation observed in skin lesions. Previous studies have revealed abnormal gene expression patterns, DNA methylation status, and cytokine secretion of MSCs in psoriatic skin lesions, as well as some gene expression abnormalities related to inflammation and angiogenesis. We further verified the gene and protein expressions of inflammation-related lipopolysaccharide-induced tumor necrosis factor-alpha transcription factor (LITAF), dual-specificity protein phosphatase 1 (DUSP1), and angiogenesis-related hematopoietically expressed homeobox (HHEX) in MSCs derived from the skin lesions of psoriasis patients...
2015: Genetics and Molecular Research: GMR
Tiago Torres, Inês Raposo, Manuela Selores
Psoriasis is a chronic, immune-mediated inflammatory disorder associated with systemic inflammation and a significantly increased risk of cardiovascular disease. Common pathologic mechanisms are likely involved in the pathogenesis of psoriasis and atherosclerosis, including similar inflammatory cytokine profiles and proinflammatory cell types. The hypothesis that aggressive treatment of skin inflammation may decrease the risk of developing atherosclerosis and consequently cardiovascular disease is currently a focus of major attention...
April 2016: American Journal of Clinical Dermatology
Olga Addimanda, Niccolò Possemato, Andrea Caruso, Nicolò Pipitone, Carlo Salvarani
Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting peripheral and axial joints, usually associated with psoriasis (PsO) and involving various systems and organs (eye inflammation, such as uveitis; and involvement of nail and enthesis), and it usually requires a multidisciplinary treatment approach. Tumor necrosis factor-α (TNF-α) is overexpressed in psoriatic synovium and skin plaques and its selective inhibition by anti-TNF-α agents has been demonstrated to reduce TNF-α levels in the articular environment, reversing the synovial hyperproliferative phenotype...
November 2015: Journal of Rheumatology. Supplement
S Y Zhong, Y Y Dong, D X Liu, D H Xu, S X Xiao, H L Chen, M G Kong
BACKGROUND: Cold atmospheric plasma (CAP) has shown promise for wound healing, although little is understood of the underpinning mechanisms. Little has been reported so far of its potential use in the treatment of immune-mediated diseases such as psoriasis. OBJECTIVES: To study CAP-induced cell death and cytokine release in human keratinocytes as a first assessment of possible CAP use for psoriasis. METHODS: Using a CAP generator free of energetic ions, we observed its effects on keratinocytes in terms of morphology, cell viability and apoptosis, intracellular and mitochondrial reactive oxygen species (ROS), lysosomal integrity and mitochondrial membrane potential; and on secretion and expression of eight cytokines at protein and gene levels...
March 2016: British Journal of Dermatology
Haley B Naik, Balaji Natarajan, Elena Stansky, Mark A Ahlman, Heather Teague, Taufiq Salahuddin, Qimin Ng, Aditya A Joshi, Parasuram Krishnamoorthy, Jenny Dave, Shawn M Rose, Julia Doveikis, Martin P Playford, Ronald B Prussick, Alison Ehrlich, Mariana J Kaplan, Benjamin N Lockshin, Joel M Gelfand, Nehal N Mehta
OBJECTIVE: To understand whether directly measured psoriasis severity is associated with vascular inflammation assessed by (18)F-fluorodeoxyglucose positron emission tomography computed tomography. APPROACH: In-depth cardiovascular and metabolic phenotyping was performed in adult psoriasis patients (n=60) and controls (n=20). Psoriasis severity was measured using psoriasis area severity index. Vascular inflammation was measured using average aortic target-to-background ratio using (18)F-fluorodeoxyglucose positron emission tomography computed tomography...
December 2015: Arteriosclerosis, Thrombosis, and Vascular Biology
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