Altered Expression of Angiopoietins and Tie2 Endothelium Receptor in Psoriasis

Abstract

Psoriasis is a chronic inflammatory skin disease in which epidermal proliferation is closely associated with excessive microvascular expansion within the papillary dermis. Angiopoietins have recently been identified as the major ligands of the endothelial- specific receptor Tie2. Angiopoietin 1 induces Tie2 signaling as a receptor activator and maintains blood vessel formation, whereas angiopoietin 2 destabilizes vessels by blocking Tie2 signaling as an antagonist of angiopoietin 1 and acts with vascular endothelial growth factor to initiate angiogenesis. In this study we examined the potential role of angiopoietins and the Tie2 receptor in vascular changes of psoriasis. Angiopoietin 1, angiopoietin 2, and Tie2 were upregulated in involved psoriasis skin compared to uninvolved psoriasis skin, healthy skin, and chronic spongiotic dermatitis skin. Angiopoietin 1 was expressed by stromal cells in the highly vascularized papillary dermis of involved psoriasis skin. Angiopoietin 2 was expressed by endothelial cells in the vicinity of the proliferating epidermis that abundantly expressed vascular endothelial growth factor. Vascular endothelial growth factor and basic fibroblast growth factor, which were overexpressed in involved psoriasis skin, enhanced angiopoietin 2 and Tie2 expression in dermal microvascular endothelial cell cultures. Thus, our findings suggest that upregulation of angiopoietin 1, angiopoietin 2, and Tie2 is closely associated with the development of microvascular proliferation in psoriasis, and that the angiopoietin-Tie2 system may act coordinately with vascular endothelial growth factor and basic fibroblast growth factor to promote neovascularization in psoriasis. Moreover, successful antipsoriatic treatment was accompanied by noticeable reduction of angiopoietin 2 expression, suggesting that alteration of angiopoietin 2 expression may be particularly important in controlling vascular proliferation in the treatment of psoriasis.

Angiopoietin/Tie2 Signaling Transforms Capillaries into Venules Primed for Leukocyte Trafficking in Airway Inflammation

“…[37][38][39][40] Interestingly, Ang1 and Ang2 were produced by different cellular sources-neutrophils and endothelial cells, respectively. We find this interesting because it may suggest that neutrophil Ang1 could play a role in regulating the vascular function/phenotype in various conditions of inflammation involving neutrophil influx.…”

Structure of the Extracellular Domain of Tie Receptor Tyrosine Kinases and Localization of the Angiopoietin-binding Epitope

“…Furthermore, overexpression of Tie2 has been observed in a wide range of diseases including psoriasis (21,22), pulmonary hypertension (23,24), infantile hemangiomas (25), and different cancers (26). Ang/ Tie2 signaling has been studied extensively and is known to * The costs of publication of this article were defrayed in part by the payment activate several downstream pathways that ultimately result in endothelial cell survival and cell migration (4).…”

Angiogenesis in cutaneous disease: Part II

“…120 Ang1 is highly expressed by stromal cells in the papillary dermis of psoriatic skin and is proposed to help maintain and stabilize newly formed vessels. 120,121 Ang2 is also expressed highly in the papillary dermis; however, its signal is limited to the endothelial cells. 120 In one study, five psoriatic patients treated with psoralen plus ultraviolet A light phototherapy and two patients treated with tazarotene for 8 weeks resulting in clinical improvement were shown to have decreased Ang1, Ang2, and Tie2 mRNA levels in involved skin.…”

“…120,121 Ang2 is also expressed highly in the papillary dermis; however, its signal is limited to the endothelial cells. 120 In one study, five psoriatic patients treated with psoralen plus ultraviolet A light phototherapy and two patients treated with tazarotene for 8 weeks resulting in clinical improvement were shown to have decreased Ang1, Ang2, and Tie2 mRNA levels in involved skin. 120 Sirolimus has been used both systemically and topically to treat psoriasis.…”

“…120 In one study, five psoriatic patients treated with psoralen plus ultraviolet A light phototherapy and two patients treated with tazarotene for 8 weeks resulting in clinical improvement were shown to have decreased Ang1, Ang2, and Tie2 mRNA levels in involved skin. 120 Sirolimus has been used both systemically and topically to treat psoriasis. Although systemic sirolimus alone proved to be ineffective in treating severe psoriasis, it was used successfully in combination with subtherapeutic levels of cyclosporine in order to limit nephrotoxicity.…”