Vol 24, No 4 (2018)
Review paper
Published online: 2018-12-05
The role of VEGF in psoriasis: an update
DOI: 10.5603/AA.2018.0019
Acta Angiologica 2018;24(4):134-140.
Abstract
Psoriasis is a common, chronic immune-mediated multifactorial skin disease. In its pathogenesis altered differentiation
and hyperproliferation of keratinocytes, dysregulation of immunological cell functions, together with
abnormal angiogenesis are involved. Angiogenesis is defined as the formation of new blood vessels from the
pre-existing vascular bed. This complex and multistep process is regulated by different factors among which
vascular endothelial growth factor (VEGF) is considered to be the most important. The aim of this paper is
a review of the current literature considering the role of vascular endothelial growth factor in psoriasis. Many
studies have focused on the role of VEGF in psoriasis and revealed its increased serum and tissue levels which
correlated with disease severity. Recent data indicate that VEGF is not only responsible for angiogenesis, but
also regulates keratinocyte differentiation. Moreover, it has been suggested that vascular endothelial growth
factor could be a link between psoriasis and its comorbidities. So far, there are single clinical cases that reported
clearance of psoriasis after anti-VEGF therapy. Therefore, the VEGF pathway might be a potential new therapeutic
alternative leading to improvement of psoriasis. However, further clinical studies are needed to evaluate
the efficacy and safety of this therapy in psoriasis.
Keywords: psoriasisangiogenesisVEGF
References
- Flisiak I, Zaniewski P, Rogalska M, et al. Effect of psoriasis activity on VEGF and its soluble receptors concentrations in serum and plaque scales. Cytokine. 2010; 52(3): 225–229.
- Wang X, Sun X, Qu X, et al. Overexpressed fibulin-3 contributes to the pathogenesis of psoriasis by promoting angiogenesis. Clin Exp Dermatol. 2018 [Epub ahead of print].
- Ogawa E, Sato Y, Minagawa A, et al. Pathogenesis of psoriasis and development of treatment. J Dermatol. 2018; 45(3): 264–272.
- De Rosa G, Mignogna C. The histopathology of psoriasis. Reumatismo. 2007; 59 Suppl 1: 46–48.
- Heidenreich R, Röcken M, Ghoreschi K. Angiogenesis drives psoriasis pathogenesis. Int J Exp Pathol. 2009; 90(3): 232–248.
- Sankar L, Arumugam D, Boj S, et al. Expression of angiogenic factors in psoriasis vulgaris. J Clin Diagn Res. 2017; 11(3): EC23–EC27.
- Malecic N, Young HS. Excessive angiogenesis associated with psoriasis as a cause for cardiovascular ischaemia. Exp Dermatol. 2017; 26(4): 299–304.
- Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003; 9(6): 669–676.
- Holmes K, Roberts OLl, Thomas AM, et al. Vascular endothelial growth factor receptor-2: structure, function, intracellular signalling and therapeutic inhibition. Cell Signal. 2007; 19(10): 2003–2012.
- Detmar M. The role of VEGF and thrombospondins in skin angiogenesis. J Dermatol Sci. 2000; 24 Suppl 1: S78–S84.
- Namiecińska M, Marciniak K, Nowak JZ. [VEGF as an angiogenic, neurotrophic, and neuroprotective factor]. Postepy Hig Med Dosw (Online). 2005; 59: 573–583.
- Skóra J, Biegus J, Pupka A, et al. Molecular basics of angiogenesis. Postepy Hig Med Dosw (Online). 2006; 60: 410–415.
- Honorati MC, Cattini L, Facchini A. IL-17, IL-1beta and TNF-alpha stimulate VEGF production by dedifferentiated chondrocytes. Osteoarthritis Cartilage. 2004; 12(9): 683–691.
- Hori R, Nakagawa T, Yamamoto N, et al. Role of prostaglandin E receptor subtypes EP2 and EP4 in autocrine and paracrine functions of vascular endothelial growth factor in the inner ear. BMC Neurosci. 2010; 11: 35.
- Yamazaki Y, Morita T. Molecular and functional diversity of vascular endothelial growth factors. Mol Divers. 2006; 10(4): 515–527.
- Marina ME, Roman II, Constantin AM, et al. VEGF involvement in psoriasis. Clujul Med. 2015; 88(3): 247–252.
- Veikkola T, Karkkainen M, Claesson-Welsh L, et al. Regulation of angiogenesis via vascular endothelial growth factor receptors. Cancer Res. 2000; 60(2): 203–212.
- Herzog B, Pellet-Many C, Britton G, et al. VEGF binding to NRP1 is essential for VEGF stimulation of endothelial cell migration, complex formation between NRP1 and VEGFR2, and signaling via FAK Tyr407 phosphorylation. Mol Biol Cell. 2011; 22(15): 2766–2776.
- Parker MW, Linkugel AD, Goel HL, et al. Structural basis for VEGF-C binding to neuropilin-2 and sequestration by a soluble splice form. Structure. 2015; 23(4): 677–687.
- Ng YS, Krilleke D, Shima DT. VEGF function in vascular pathogenesis. Exp Cell Res. 2006; 312(5): 527–537.
- Koczy-Baron E, Kasperska-Zając A. [The role of vascular endothelial growth factor in inflammatory processes]. Postepy Hig Med Dosw (Online). 2014; 68: 57–65.
- Detmar M, Brown LF, Schön MP, et al. Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice. J Invest Dermatol. 1998; 111(1): 1–6.
- Xia YP, Li B, Hylton D, et al. Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis. Blood. 2003; 102(1): 161–168.
- Bae ON, Noh M, Chun YJ, et al. Keratinocytic Vascular Endothelial Growth Factor as a Novel Biomarker for Pathological Skin Condition. Biomolecules & Therapeutics. 2015; 23(1): 12–18.
- Simonetti O, Lucarini G, Goteri G, et al. VEGF is likely a key factor in the link between inflammation and angiogenesis in psoriasis: results of an immunohistochemical study. Int J Immunopathol Pharmacol. 2006; 19(4): 751–760.
- Rashed H, El-Bary EA. Immunohistochemical evaluation of VEGF, survivin, bcl-2 protein and iNOS in the pathogenesis of psoriasis. Egyptian Journal of Pathology. 2012; 32(1): 91–98.
- Liew SC, Das-Gupta E, Chakravarthi S, et al. Differential expression of the angiogenesis growth factors in psoriasis vulgaris. BMC Res Notes. 2012; 5: 201.
- Moustou AE, Alexandrou P, Stratigos AJ, et al. Expression of lymphatic markers and lymphatic growth factors in psoriasis before and after anti-TNF treatment. An Bras Dermatol. 2014; 89(6): 891–897.
- Man XY, Yang XH, Cai SQ, et al. Immunolocalization and expression of vascular endothelial growth factor receptors (VEGFRs) and neuropilins (NRPs) on keratinocytes in human epidermis. Mol Med. 2006; 12(7-8): 127–136.
- Man XY, Yang XH, Cai SQ, et al. Overexpression of vascular endothelial growth factor (VEGF) receptors on keratinocytes in psoriasis: regulated by calcium independent of VEGF. J Cell Mol Med. 2008; 12(2): 649–660.
- Jiang M, Li B, Zhang J, et al. Vascular endothelial growth factor driving aberrant keratin expression pattern contributes to the pathogenesis of psoriasis. Exp Cell Res. 2017; 360(2): 310–319.
- Nielsen HJ, Christensen IJ, Svendsen MN, et al. Elevated plasma levels of vascular endothelial growth factor and plasminogen activator inhibitor-1 decrease during improvement of psoriasis. Inflamm Res. 2002; 51(11): 563–567.
- Xuan Ml, Lu Cj, Han L, et al. Circulating levels of inflammatory cytokines in patients with psoriasis vulgaris of different Chinese medicine syndromes. Chinese Journal of Integrative Medicine. 2014; 21(2): 108–114.
- Meki ARMA, Al-Shobaili H. Serum vascular endothelial growth factor, transforming growth factor β1, and nitric oxide levels in patients with psoriasis vulgaris: their correlation to disease severity. J Clin Lab Anal. 2014; 28(6): 496–501.
- Andrys C, Borska L, Pohl D, et al. Angiogenic activity in patients with psoriasis is significantly decreased by Goeckerman's therapy. Arch Dermatol Res. 2007; 298(10): 479–483.
- Akman A, Dicle O, Yilmaz F, et al. Discrepant levels of vascular endothelial growth factor in psoriasis patients treated with PUVA, Re-PUVA and narrow-band UVB. Photodermatol Photoimmunol Photomed. 2008; 24(3): 123–127.
- Weidemann AK, Crawshaw AA, Byrne E, et al. Vascular endothelial growth factor inhibitors: investigational therapies for the treatment of psoriasis. Clin Cosmet Investig Dermatol. 2013; 6: 233–244.
- Barile S, Medda E, Nisticò L, et al. Vascular endothelial growth factor gene polymorphisms increase the risk to develop psoriasis. Exp Dermatol. 2006; 15(5): 368–376.
- Yamamoto M, Tada Y, Asahina A, et al. Severe generalized pustular psoriasis accompanied by bullae formation with increased serum vascular endothelial growth factor level. J Dermatol. 2012; 39(2): 183–185.
- Creamer D, Allen M, Jaggar R, et al. Mediation of systemic vascular hyperpermeability in severe psoriasis by circulating vascular endothelial growth factor. Arch Dermatol. 2002; 138(6): 791–796.
- Przepiera-Będzak H, Fischer K, Brzosko M. Serum levels of angiogenic cytokines in psoriatic arthritis and SAPHO syndrome. Pol Arch Med Wewn. 2013; 123(6): 297–302.
- Sudhesan A, Rajappa M, Chandrashekar L, et al. Vascular endothelial growth factor (VEGF) gene polymorphisms (rs699947, rs833061, and rs2010963) and psoriatic risk in South Indian Tamils. Hum Immunol. 2017; 78(10): 657–663.
- Young HS, Summers AM, Read IR, et al. Interaction between genetic control of vascular endothelial growth factor production and retinoid responsiveness in psoriasis. J Invest Dermatol. 2006; 126(2): 453–459.
- Young HS, Summers AM, Bhushan M, et al. Single-nucleotide polymorphisms of vascular endothelial growth factor in psoriasis of early onset. J Invest Dermatol. 2004; 122(1): 209–215.
- Hawkes JE, Nguyen GH, Fujita M, et al. microRNAs in Psoriasis. J Invest Dermatol. 2016; 136(2): 365–371.
- Li Y, Su J, Li F, et al. MiR-150 regulates human keratinocyte proliferation in hypoxic conditions through targeting HIF-1α and VEGFA: Implications for psoriasis treatment. PLoS One. 2017; 12(4): e0175459.
- Zheng YZ, Chen CF, Jia LY, et al. Correlation between microRNA-143 in peripheral blood mononuclear cells and disease severity in patients with psoriasis vulgaris. Oncotarget. 2017; 8(31): 51288–51295.
- Xu Y, Ji Y, Lan X, et al. miR‑203 contributes to IL‑17‑induced VEGF secretion by targeting SOCS3 in keratinocytes. Mol Med Rep. 2017; 16(6): 8989–8996.
- Canavese M, Altruda F, Ruzicka T, et al. Vascular endothelial growth factor (VEGF) in the pathogenesis of psoriasis--a possible target for novel therapies? J Dermatol Sci. 2010; 58(3): 171–176.
- Akman A, Yilmaz E, Mutlu H, et al. Complete remission of psoriasis following bevacizumab therapy for colon cancer. Clin Exp Dermatol. 2009; 34(5): e202–e204.
- Datta-Mitra A, Riar NK, Raychaudhuri SP. Remission of psoriasis and psoriatic arthritis during bevacizumab therapy for renal cell cancer. Indian J Dermatol. 2014; 59(6): 632.
- Narayanan S, Callis-Duffin K, Batten J, et al. Improvement of psoriasis during sunitinib therapy for renal cell carcinoma. Am J Med Sci. 2010; 339(6): 580–581.
- Fournier C, Tisman G. Sorafenib-associated remission of psoriasis in hypernephroma: case report. Dermatol Online J. 2010; 16(2): 17.
- Kuang YH, Lu Y, Liu YK, et al. Topical Sunitinib ointment alleviates Psoriasis-like inflammation by inhibiting the proliferation and apoptosis of keratinocytes. Eur J Pharmacol. 2018; 824: 57–63.