Angiogenesis drives psoriasis pathogenesis

Abstract

Summary Psoriasis pathogenesis is closely associated with disease‐inducing Th1 and Th17 cells. Yet, several studies suggest that aberrant keratinocyte or endothelial cell signalling significantly contributes to disease manifestation. Histological hallmarks of psoriatic skin include the infiltration of multiple immune cells, keratinocyte proliferation and increased dermal vascularity. Formation of new blood vessels starts with early psoriatic changes and disappears with disease clearance. Several angiogenic mediators like vascular endothelial growth factor, hypoxia‐inducible factors, angiopoietins and pro‐angiogenic cytokines, such as tumour necrosis factor (TNF), interleukin (IL)‐8 and IL‐17, are up‐regulated in psoriasis development. Contact‐ and mediator‐dependent factors derived from keratinocytes, mast cells and immune cells may contribute to the strong blood vessel formation of psoriasis. New technologies and experimental models provide new insights into the role of angiogenesis in psoriasis pathogenesis. Interestingly, many therapies target not only immune cells, but also protein structures of endothelial cells. Here we summarize the role of pro‐angiogenic factors in psoriasis development and discuss angiogenesis as a potential target of novel therapies.

Vascular Normalization as a Therapeutic Strategy for Malignant and Nonmalignant Disease

“…Current models suggest that angiogenesis is required for the induction of psoriatic pathology and maintains the immune and inflammatory processes that drive psoriasis (Heidenreich et al 2009). …”

“…Underlying psoriatic angiogenesis, several proangiogenic factors including tumor necrosis factor-a (TNF-a), VEGF, HIFs, Interleukin (IL)-8, and angiopoietins, are all enriched in psoriatic skin (Heidenreich et al 2009). As abnormal angiogenesis is considered to be the key to the initiation and progression of psoriasis, several antiangiogenic therapies have been developed to treat psoriasis.…”

Pathogenesis of Psoriasis: The Role of Pro-Inflammatory Cytokines Produced by Keratinocytes

“…The formation of new blood vessels starts with early psoriatic changes and disappears with disease clearance. Several angiogenic mediators like VEGF, hypoxia inducible factors, angiopoietins and pro-angiogenic cytokines, such as TNF-, IL-8 and IL-17, are involved in psoriasis development (Heidenreich et al, 2009). Interestingly, already in uninvolved, nonlesional skin significant over-expression of several VEGF isoforms was observed in patients as compared to healthy skin of normal volunteers (Henno et al, 2009).…”

“…These findings suggest that angiogenesis is also one of the key features in the pathogenesis of psoriasis and various recent studies focused on the identification and role of pro-angiogenic mediators in psoriatic skin. In general, angiogenesis is tightly regulated by a balance between pro-and anti-angiogenic mediators (Heidenreich et al, 2009). VEGF, hypoxia-inducible factor-1 (HIF-1 ), TNF-, IL-8 and angiopoietins are considered to be the main players responsible for the increased vessel formation in psoriasis (Creamer et al, 2002;Heidenreich et al, 2008).…”

Effects of crude extracts of various pigments isolated from Spirulina platensis and Chlorella vulgaris on the angiogenesis of chick embryo chorioallantoic membrane (cam)

“…Further, some chemicals such as heparin and endostatin are responsible for stopping the process of cell repairing and are also responsible for the inhibition of the synthesis of stimulatory chemicals, these inhibitory chemicals are known as angiogenesis inhibitors (Zhao-Na et al, 2015;Jin-Yan et al, 2016). Uncontrolled angiogenesis is a major contributor in a number of diseases such as arthritis, diabetes-related blindness, psoriasis, tumor growth and metastasis (Heidenreich et al, 2009;Gayetsky et al, 2014). Anti-angiogenic compounds would be useful in treating diseases caused by uncontrolled angiogenesis.…”