Abstract
Background:
In recent years, more and more attention has been paid to the role of skin microcirculation in the pathogenesis of psoriasis. The vascular network of the skin is mainly distributed in the dermis and the subcutaneous fat layer join. The microvessels are composed of terminal arterioles, arteriovenous capillaries, and postcapillary venules. Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of psoriasis by promoting angiogenesis. The purpose of this study is to evaluate the relationship between serum VEGF and psoriasis vulgaris.
Methods:
Embase, CENTRAL, PubMed, China Biology Medicine Database, China National Knowledge Database, Wan Fang Database, and Chong Qing VIP Database will be searched to collect case-control studies and cohort studies and evaluate the relationship between serum VEGF and psoriasis vulgaris. The search time limits will be from the establishment of the database to December 2020. Two researchers will independently screen the studies, extract data, and evaluate the risk of bias of the studies. The Meta-analysis will be carried out with the RevMan5.3 software. The quality of all included studies will be evaluated by the Newcastle-Ottawa scale.
Results:
This study will evaluate the relationship between serum VEGF and the pathogenesis of psoriasis vulgaris.
Conclusion:
This study will provide a theoretical basis for the pathogenesis of psoriasis vulgaris.
OSF registration number:
DOI 10.17605/OSF.IO/6DV8P
Keywords: protocol, psoriasis vulgaris, systematic review, vascular endothelial growth factor
1. Introduction
Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population.[1] In recent years, more and more attention has been paid to the role of skin microcirculation in the pathogenesis of psoriasis. The vascular network of the skin is mainly distributed in the dermis and the subcutaneous fat layer join. The microvessels are composed of terminal arterioles, arteriovenous capillaries, and postcapillary venules.[2,3]
The change of microcirculation is an important histopathological change in psoriasis, which results in structural and functional changes under the action of various pathogenic factors, resulting in the occurrence and maintenance of inflammatory reaction. The changes of microcirculation can be used as an effective index to evaluate the severity of the disease, the efficacy of drugs and the monitoring of the disease.[2] Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of psoriasis by promoting angiogenesis.[4,5] Because of its complex pathogenesis, psoriasis can not be cured completely at present. The main purpose of treatment is to control and stabilize the disease, slow down the development process, reduce clinical symptoms such as erythema, scale, plaque thickening, and pruritus, reduce short-term and long-term adverse reactions, control psoriasis-related complications, and improve patients’ quality of life.[6]
Psoriatic lesions are characterized by a high degree of changes in the vascular network, that is, a large number of dilated, tortuous, and highly permeable skin vessels. The secretion of a variety of angiogenic growth factors promotes the expansion of the vascular network of psoriatic skin cells. Angiogenesis in psoriasis is closely related to vascular endothelial activation, angiogenesis, inflammation, and skin lesions.[7] The formation of skin blood vessels includes vasculogenesis and angiogenesis,[8] and vasculogenesis is a key factor in the pathogenesis of psoriasis. VEGF is the mediator of pathological angiogenesis and is overexpressed in the skin of patients with psoriasis.[9] VEGF not only promotes skin angiogenesis in patients with psoriasis, but also acts as an autocrine regulator of epidermal hyperplasia,[10] driving psoriasis keratin imbalance and epidermal hyperplasia,[11] thus forming a characteristic lesion of psoriasis.
Besides, VEGF promotes the formation of cell adhesion molecules in capillaries and increases vascular permeability, resulting in the migration of leukocytes to the skin of patients with psoriasis. This process leads to the increase of oxygen consumption and the activation of angiogenic transcription factors, which makes it difficult to heal the angiogenesis and inflammation of psoriasis repeatedly.[4] The correlation study on the mechanism of angiogenesis in psoriasis vulgaris showed that the expression of VEGF in skin lesions and serum of patients with psoriasis vulgaris was significantly higher than that in normal controls, suggesting that VEGF may play an important role in angiogenesis and inflammation of psoriasis and can be used as an index to evaluate the severity of psoriasis vulgaris.[7] Related studies also show that VEGF may be an important index to judge the activity of psoriasis vulgaris.[4,12,13]
2. Methods
This protocol has been registered in the Open Science Framework. The system review will be submitted to peer-reviewed journals. This protocol will be based on the preferred reporting items for systematic reviews and meta-analysis protocols 2015 statement.[14]
2.1. Inclusion criteria
2.1.1. Type of study
All case-control studies and cohort studies that evaluate the relationship between serum VEGF and psoriasis vulgaris.
2.1.2. Types of participants
Patients diagnosed with psoriasis vulgaris, regardless of nationality, race, gender, age, and course of the disease.
2.1.3. Exposure factors
The levels of serum VEGF.
2.1.4. Outcomes
The expression levels of serum VEGF and its correlation with psoriasis vulgaris.
2.2. Exclusion criteria
The exclusion criteria will be as follows: duplicate literature; literature with only abstracts but no full text; literature with incomplete data; studies involving animal experiments; patients who have taken steroids within the preceding two weeks and/or taken retinoids or topical steroids within the preceding week.
2.3. Electronics searches
Embase, CENTRAL, PubMed, China Biology Medicine Database, China National Knowledge Database, Wan Fang Database, and Chong Qing VIP Database will be searched to collect case-control studies and cohort studies and evaluate the relationship between serum VEGF and psoriasis vulgaris. The search time limit will be from the establishment of the database to December 2020.
2.4. Search strategy
The keywords of the search will include ‘Vascular Endothelial Growth Factors’, ‘Vascular Endothelial Growth Factor’, ‘VEGF’, ‘Vascular Endothelial Growth Factor A’, ‘Vascular Endothelial Growth Factor B’, ‘Vascular Endothelial Growth Factor C’, ‘Vascular Endothelial Growth Factor D’; ‘psoriasis’, ‘psoriasis vulgaris’, ‘plaque psoriasis’, ‘guttate psoriasis’; ‘Case-Control Studies’, ‘Case-Control Study’, ‘Studies, Case-Control’, ‘Study, Case-Control’; ‘Cohort Studies’, ‘Cohort Study’, ‘Studies, Cohort’, ‘Study, Cohort’.
2.5. Data extraction and management
Two researchers will independently screen the studies, extract data, and perform crosschecks. Differences will be solved through discussion with a third researcher. The data extraction includes the first author, publication time, country, sample size, VEGF detection methods, the VEGF types, outcome measure (the expression levels of serum VEGF and its correlation with psoriasis vulgaris).
2.6. Data synthesis and analysis
Meta-analysis will be performed with RevMan V.5.3 software. Standardized mean difference will be used for continuous variables, and the 95% CI will be given for each effect size.
2.7. Assessment of heterogeneity
The studies’ heterogeneity will be assessed by using the I2 index. If the I2 < 50%, studies will not be considered heterogeneous, and the fixed-effects model will be used for meta-analysis. If the I2 > 50%, we will analyse the cause of the heterogeneity by using subgroup and sensitivity analysis, and the random-effects model will be used for meta-analysis.
2.7.1. Subgroup analysis
If there is significant heterogeneity in the included studies, we will conduct subgroup analysis according to the study types, VEGF detection methods, and the VEGF types.
2.7.2. Sensitivity analysis
Sensitivity analysis will be conducted to check the stability of the outcome by rejecting low-quality studies.
2.7.3. Assessment of publication bias
The funnel plots will be used to assess publication bias.
2.7.4. Quality assessment
The quality of the included study will be assessed by the Newcastle-Ottawa scale (NOS).[15,16] The NOS ranges between zero up to nine stars. It will evaluate the quality of each study from the following three aspects: the selection of the study groups, the comparability of the groups, the exposure of case-control studies, and the outcome of cohort studies. The total scores are categorized into three groups: very high risk of bias (0 to 3 NOS points), high risk of bias (4 to 6), and low risk of bias (7 to 9).[17]
3. Discussion
Several previous clinical studies have reported the relationship between serum VEGF and psoriasis,[18–20] but there are few systematic reviews to explore the relationship between serum VEGF and psoriasis vulgaris. In this study, we will systematically evaluate the relationship between serum VEGF and the pathogenesis of psoriasis vulgaris through a comprehensive search of the literature. The results of this study will summarize the latest evidence about the relationship between serum VEGF and psoriasis vulgaris. This study will not only provide useful evidence for patients and clinicians but also provide a theoretical basis for the pathogenesis of psoriasis vulgaris.
However, this systematic review may have several limitations. First of all, the databases we searched are limited and do not represent all the studies. Secondly, we will include both case-control studies and cohort studies, which may result in substantial heterogeneity. Third, there are a variety of methods for the detection of serum VEGF, which will become a factor in heterogeneity. We hope that this systematic review and Meta analysis can provide reliable evidence for the association between serum VEGF and psoriasis vulgaris.
Author contributions
Conceptualization: Juan Gong, Dongwei Qi.
Investigation: Hua Yang, Xueyong Tang.
Supervision: Juan Gong, Dongwei Qi.
Writing – original draft: Hua Yang, Xueyong Tang.
Writing – review & editing: Hua Yang, Dongwei Qi.
Footnotes
Abbreviations: CI = confidence interval, MeSH = Medical Subject Headings, NOS = Newcastle-Ottawa scale, OSF = Open Science Framework, SMD = standardized mean difference, VEGF = Vascular endothelial growth factor.
How to cite this article: Gong J, Yang H, Qi D, Tang X. The association of serum vascular endothelial growth factor levels and psoriasis vulgaris: a protocol for systematic review and meta-analysis. Medicine. 2020;99:33(e21565).
This study was supported by the Scientific Research Project of Chongqing Science and Health Joint Traditional Chinese Medicine (Grant No. 2019ZY023158), National Natural Science Foundation of China (Grant No. 81704091), China Postdoctoral Science Foundation (Grant No. 2019M653348), Natural Science Foundation of Chongqing (Grant No. cstc2019jcyj-msxmX0757), and Scientific Research Project of Chongqing Science and Health Joint Traditional Chinese Medicine (Grant No. ZY201802142).
Ethics and dissemination: Original data will not be collected, and no ethical approval will be required.
Ethics and dissemination: Raw data will not be collected and ethical approval will not be required. Original data will not be collected, and no ethical approval will be required. The review of this system will be submitted to peer-reviewed journals.
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are publicly available. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.
References
- [1].Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 2008;58:826–50. [DOI] [PubMed] [Google Scholar]
- [2].Fei W, Tang H, Yang S, et al. Changes of cutaneous microcirculatory in psoriasis. Chin J Derm Venereol 2013;32:714–7. [Google Scholar]
- [3].McLafferty E, Hendry C, Alistair F. The integumentary system: anatomy, physiology and function of skin. Nurs Stand 2012;27:35–42. [DOI] [PubMed] [Google Scholar]
- [4].Marina ME, Roman II, Constantin AM, et al. VEGF involvement in psoriasis. Clujul Med 2015;88:247–52. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [5].Chiricozzi A, Romanelli P, Volpe E, et al. Scanning the immunopathogenesis of psoriasis. Int J Mol Sci 2018;19:179. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [6].Committee on Psoriasis, Chinese Society of Dermatology. Guideline for the diagnosis and treatment of psoriasis in China (2018 complete edition). Chin J Dermatol 2019;52:667–710. [Google Scholar]
- [7].Akhtar T, Wani WY, Kamal MA, et al. Role of angiogenic growth factors in psoriasis: a review. Curr Drug Metab 2018;19:910–6. [DOI] [PubMed] [Google Scholar]
- [8].Wang C, Yin R, Li Z, et al. Characteristics of skin blood vessel’ development and formation. Chin J Lepr Skin Dis 2016;32:382–4. [Google Scholar]
- [9].Malecic N, Young HS. Excessive angiogenesis associated with psoriasis as a cause for cardiovascular ischaemia. Exp Dermatol 2017;26:299–304. [DOI] [PubMed] [Google Scholar]
- [10].Elias PM, Arbiser J, Brown BE, et al. Epidermal vascular endothelial growth factor production is required for permeability barrier homeostasis, dermal angiogenesis, and the development of epidermal hyperplasia: implications for the pathogenesis of psoriasis. Am J Pathol 2008;173:689–99. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [11].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;360:310–9. [DOI] [PubMed] [Google Scholar]
- [12].Chawla N, Kataria SP, Aggarwal K, et al. Significance of vascular endothelial growth factor and CD31 and morphometric analysis of microvessel density by CD31 receptor expression as an adjuvant tool in diagnosis of psoriatic lesions of skin. Indian J Pathol Microbiol 2017;60:189–95. [DOI] [PubMed] [Google Scholar]
- [13].Sankar L, Arumugam D, Boj S, et al. Expression of Angiogenic Factors in Psoriasis Vulgaris. J Clin Diagn Res 2017;11:Ec23–ec27. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [14].Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015;4:1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [15].Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603–5. [DOI] [PubMed] [Google Scholar]
- [16].Wells G, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp [cited 2009 Oct 19]. [Google Scholar]
- [17].Lo CK-L, Mertz D, Loeb M. Newcastle-Ottawa Scale: comparing reviewers’ to authors’ assessments. BMC Med Res Methodol 2014;14:45. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [18].Meki AR, Al-Shobaili H. Serum vascular endothelial growth factor, transforming growth factor beta1, and nitric oxide levels in patients with psoriasis vulgaris: their correlation to disease severity. J Clin Lab Anal 2014;28:496–501. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [19].Shahidi-Dadras M, Haghighatkhah HR, Abdollahimajd F, et al. Correlation between vascular endothelial growth factor and subclinical atherosclerosis in patients with psoriasis. Int J Dermatol 2016;55:52–9. [DOI] [PubMed] [Google Scholar]
- [20].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;52:225–9. [DOI] [PubMed] [Google Scholar]