Levels of endothelial cell stimulating angiogenesis factor and vascular endothelial growth factor are elevated in psoriasis

Abstract

Neovascularization appears to play an early and important part in the evolution of psoriatic plaques. We studied the distribution and production of two known angiogenesis factors, endothelial cell stimulating angiogenesis factor (ESAF) and vascular endothelial growth factor (VEGF), in the skin of patients with chronic plaque psoriasis and normal control subjects. Our results showed that tissue levels of ESAF and VEGF were significantly elevated in involved as compared with normal control skin (P = 0.006 and P < 0. 0001, respectively). Tissue levels of ESAF and VEGF were also raised in involved skin as compared with uninvolved skin in patients with psoriasis (P = 0.001 and P < 0.0001, respectively). Tissue levels of ESAF and VEGF in plaques of psoriasis correlated closely with the clinical severity of psoriasis (r = 0.6 and r = 0.9, respectively). Serum levels of ESAF and VEGF were significantly raised in patients with psoriasis as compared with control subjects (P = 0.001 and P = 0.02, respectively). In vitro culture studies revealed that ESAF is produced by both keratinocytes and fibroblasts in approximately equal quantities in normal skin, whereas VEGF is secreted predominately by keratinocytes. A similar pattern is seen in both involved and uninvolved skin of patients with psoriasis. However, there is increased secretion of both factors in keratinocytes and fibroblasts from involved and uninvolved skin as compared with normal control skin (P < 0.001). The increased levels and secretion in plaques of psoriasis of two molecules, ESAF and VEGF, known to promote new blood vessel formation, suggest a pathogenetic role for them in this disease.

Stimulation of lymphangiogenesis via VEGFR-3 inhibits chronic skin inflammation

“…The VEGF-A level is a good marker for inflammation in human psoriasis and in the K14-VEGF-A mouse model of chronic skin inflammation (Bhushan et al, 1999;Kunstfeld et al, 2004;Halin et al, 2007Halin et al, , 2008. In agreement with an overall improvement of inflammation, VEGF-A protein levels were significantly lower (P < 0.05) in VEGF-A+C mice than in VEGF-A Tg mice (Fig.…”

Comano's (Trentino) thermal water interferes with the expression and secretion of vascular endothelial growth factor-A protein isoforms by cultured human psoriatic keratinocytes: A potential mechanism of its anti-psoriatic action

“…Further lines of evidence that we are presently gathering show that in vitro exposure to CW-DMEM also interferes with the increased expression and secretion of at least two more angiogenic cytokines, IL-1 and IL-6 (9,(12)(13)(14)(15)(16)(17)(18)(19), on the part of human psoriatic keratinocytes (unpublished data). Conceivably, such complex anti-angiogenic effects brought about by CW balneotherapy would justify, from a pathophysiological standpoint, at least part of its known beneficial effects on the clinical manifestations of psoriasis (59), and concurrently rule out the possibility that such benefits are of the placebo kind.…”

“…neutrophils, T lymphocytes, monocytes) (4,5), it has been surmised that psoriasis is an angioproliferative ailment depending upon the release of angiogenic molecules by the epidermis (6)(7)(8)(9)(10)(11). Increased amounts of several angiogenic cytokines, including transforming growth factor-· (TGF-·), tumour necrosis factor-· (TNF-·), interleukin-1 (IL-1), IL-6, IL-20, amphiregulin, plateletderived endothelial cell growth factor/thymidine phosphorylase (TP), endothelial cell stimulating angiogenesis factor (ESAF), and VEGF-A are produced and secreted by the psoriatic keratinocytes (9,(12)(13)(14)(15)(16)(17)(18)(19).…”

Vascular Endothelial Growth Factor and Angiogenesis

“…Detmar et al (1994) concluded that VEGF-A synthesis and secretion by keratinocytes in psoriasis is stimulated by TGF-␣ and EGF, since receptors for these factors are overexpressed in psoriatic skin. Serum VEGF-A concentrations are increased in patients with psoriasis (Bhushan et al, 1999), and this may reflect overproduction, either in the skin with overflow into the circulation or as a primary genetic aberration. Antiangiogenesis treatment may be a novel selective therapeutic strategy.…”