Genetic interaction between placental growth factor and vascular endothelial growth factor A in psoriasis

Abstract

Summary Background Expression of vascular endothelial growth factor A (VEGFA) is increased in chronic inflammatory skin diseases, including psoriasis, and loci for two VEGFA single nucleotide polymorphisms are associated with early‐onset psoriasis (presenting before the age of 40 years). Studies have suggested that expression of placenta growth factor (PGF) is also upregulated in cutaneous inflammation and that VEGFA‐mediated angiogenesis may be dependent on the simultaneous presence of PGF within the skin. Aim To elucidate the biological importance of PGF in psoriasis. Methods We investigated whether two commonly occurring PGF polymorphisms were associated with early‐onset psoriasis and the genetic interaction between VEGFA and PGF in psoriasis. Results We observed a significant (P = 0.04) association between rs2268614 TT and rs2268615 AA genotypes of PGF and early‐onset psoriasis. In addition, genetic complement, comprising the PGF rs2268615 AA genotype and the VEGFA −460 (rs833061) T allele, was significantly associated with the development of early‐onset psoriasis (P < 0.03). We identified that the VEGFA genotype influences PGF expression (P = 0.001) and that mean plasma levels of PGF are lower in patients with severe psoriasis compared with those with mild–moderate disease (P = 0.04). Conclusion Our observed genetic interaction between PGF and VEGFA appears relevant to psoriasis, a disease with an angiogenic basis, and may influence development of an antiangiogenic approach to treatment.

Vascular endothelial growth factor‐A as a promising therapeutic target for the management of psoriasis

“…Vascular endothelial growth factor-A (VEGF-A) is recognised not only as the main angiogenic mediator, [8] but also as a key mediator of angiogenesis in pathological processes including solid tumors and [9] intraocular neovascular syndromes. [10][11][12][13] VEGF-A is now appreciated to play a critical role in the pathogenesis of several inflammatory immune-mediated diseases including psoriasis [10,14,15] (see below).…”

Vascular Endothelial Growth Factor A VEGFA Inhibition: An Effective Treatment Strategy for Psoriasis

“…On the other hand, there is a correlation between VEGFA single-nucleotide polymorphisms (SNPs) and the severity of psoriasis. Young and others provided genetic evidence for VEGFA as a modifier gene in psoriasis by analyzing VEGFA gene SNPs in psoriasis patients and healthy individuals [ 41 , 42 ]. Overexpression of VFGFA in mouse epidermis can induce psoriasis-like disease, and angiogenesis and inflammatory cell infiltration are similar to psoriatic skin lesions.…”

Circadian rhythms in psoriasis and the potential of chronotherapy in psoriasis management

“…Angiogenesis, a key mediator of the pathogenesis of various diseases including psoriasis, is controlled by the circadian system, and maintenance of the circadian rhythms plays an important role in pathogenic angiogenesis 19,20 . Vascular endothelial growth factor A (VEGF‐A), a mediator of inflammatory angiogenesis in psoriasis, plays a major role in its pathogenesis 21–23 . Anti‐VEGF‐A treatment strategies are not licensed for the management of psoriasis, although these are widely used in cancer and ophthalmological diseases 24–26 .…”

“… 19 , 20 Vascular endothelial growth factor A (VEGF‐A), a mediator of inflammatory angiogenesis in psoriasis, plays a major role in its pathogenesis. 21 , 22 , 23 Anti‐VEGF‐A treatment strategies are not licensed for the management of psoriasis, although these are widely used in cancer and ophthalmological diseases. 24 , 25 , 26 Indeed, the anti‐tumor efficacy of VEGF‐A inhibition can be enhanced by administering treatment at a time when VEGF‐A levels are at their peak.…”