臨床および実験皮膚科学研究ジャーナル
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概要

The Role of Angiogenesis in the Pathogenesis of Psoriasis: Mechanisms and Clinical Implications

Simon Guerard and Roxane Pouliot

Psoriasis is a complex multisystemic skin disease characterized by the recurrent apparition of erythematous plaques often covered by silvery scales. In recent years, the importance attributed to angiogenesis in psoriasis by the scientific community has grown significantly. The vascular network found within these lesions is highly altered, especially in the papillary dermis which is infiltrated by a large number of tortuous and dilated capillaries. Also, endothelial cells composing these vessels are activated and express many adhesion molecules promoting leukocyte recruitment (ICAM-1, VCAM-1, Thy-1, E- and P-selectin). Thus, this pathological angiogenesis is not a mere consequence of the disease, but a key component promoting leukocyte accumulation, inflammation and therefore, skin lesions. This review presents the current understanding and the clinical implications of angiogenesis in psoriasis. Psoriatic skin cells, particularly keratinocytes, promote the expansion of the vascular network through the secretion of pro-angiogenic factors such as VEGF and angiopoietins. Moreover, pro-inflammatory cytokines such as TNF-α, which exert pro-angiogenic action as well as activation of endothelial cells, also contribute to this process. It was demonstrated by in vivo models that angiogenesis, activation of vascular endothelium, inflammation and skin lesions are all closely related in psoriasis. Indeed, angiogenesis promoted by VEGF-secreting keratinocytes leads to local inflammation and skin lesions mimicking psoriasis. From a clinical perspective, most psoriatic treatments have direct, or at least indirect, anti-angiogenic impact, suggesting that their clinical efficacy might be partly explained by these properties. Altogether, these findings identify angiogenesis and the activation of endothelial cells as novel pharmacological targets against psoriasis.