Cytokines and Venous Leg Ulcer Healing—A Systematic Review

Burian, Ewa Anna; Sabah, Lubna; Karlsmark, Tonny; Kirketerp‐Møller, Klaus; Moffatt, Christine; Thyssen, Jacob P.; Ågren, Magnus S.

doi:10.3390/ijms23126526

Cited by 24 publications

(10 citation statements)

References 99 publications

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“…Harris et al 63 VLUs. 64 In contrast, an analysis by Burian et al 65 found no significant differences in the levels of the cytokines studied and determined that the relationship between cytokine levels and ulcer healing is consequential or coincidental.…”

Section: Resultsmentioning

confidence: 97%

Evaluation of factors affecting the healing process of venous ulcers: A 12‐week longitudinal study

Mościcka,

Cwajda‐Białasik,

Jawień

et al. 2023

Wound Repair Regeneration

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The process of healing venous ulcers is complex and influenced by many factors. By identifying the risk factors that influence a slower healing process, it is possible to predict impending delays and plan an individualised care plan. We analysed our database of patients with venous ulcers and identified clinical and demographic factors that delay the healing process. The research analysed the medical records of 754 patients with VLUs at Chronic Wound Treatment Unit of the University Hospital treated between 2001 and 2019. In study, the majority (64.3%) were women, the mean age was 65.7 years. The median duration of Chronic Venous Insufficiency was 24 years, 52% patients had had the disease >20 years, and 296 (39.3%) had experienced ulceration >12 months. Most of the patients (85.8%) had comorbidities, 84% were obese. At 12‐week follow‐up, 432 of the 754 ulcers had healed. Identified independent predictors of slower ulcer healing rates: wound area greater than 8.25 cm2, location of the ulceration other than the medial ankle area, underlying disease >20 years, the presence of multiple comorbidities, depth of the ulcer, the presence of an unpleasant smell and alert pathogens. The presence of redness resulted in faster healing of VLUc. Many factors influence the healing process of venous ulceration. The results of the study can help in planning patient care and implementing appropriate early strategies to promote healing.

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Section: Resultsmentioning

confidence: 97%

Evaluation of factors affecting the healing process of venous ulcers: A 12‐week longitudinal study

Mościcka,

Cwajda‐Białasik,

Jawień

et al. 2023

Wound Repair Regeneration

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“…Angiogenesis and growth factor production is essential for diabetic wound healing. PDGF is currently the only growth factor treatment for diabetic wounds approved by FDA ( 7 ). FGF2 has been reported to contribute critically to the modulation of scar formation ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

Boosting UPR transcriptional activator XBP1 accelerates acute wound healing

Wang

et al. 2023

PNAS Nexus

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Introduction Patients suffering from large or deep wounds caused by traumatic and/or thermal injuries have significantly lower chances of recapitulating lost skin function through natural healing. We tested whether enhanced Unfolded Protein Response (UPR) by expression of a UPR transcriptional activator, X-box binding protein 1 (XBP1), can significantly promote wound repair through stimulating growth factor production and promoting angiogenesis. Methods and Results In mouse models of a second-degree thermal wound, a full-thickness traumatic wound, and a full-thickness diabetic wound, the topical gene transfer of the activated form of XBP1 (spliced XBP1, XBP1s) can significantly enhance re-epithelialization and increase angiogenesis, leading to rapid, nearly complete wound closure with intact regenerated epidermis and dermis. Over-expression of XBP1s stimulated the transcription of growth factors in fibroblasts critical to proliferation and remodelling during wound repair, including PDGF BB, FGF2, and TGFβ3. Meanwhile, the over-expression of XBP1s boosted the migration and tube formation of dermal microvascular endothelial cells in vitro. Conclusion Our functional and mechanistic investigations of XBP1-mediated regulation of wound healing processes provide novel insights into the previously undermined physiological role of the UPR in skin injuries. The finding opens an avenue to developing potential XBP1-based therapeutic strategies in clinical wound care protocols.

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“…The upregulation of inflammatory mediators and the infiltration of immune cells, including neutrophils, macrophages, and lymphocytes, into the venous wall are instrumental in the remodelling processes, endothelial dysfunction, and tissue damage, thereby amplifying ulceration risks. [17][18][19][20] Notwithstanding the established association between inflammation and varicose veins, the specific linkage between inflammatory markers and the onset of venous wounds remains ambiguous. Mendelian randomization (MR) has emerged as a potent analytical method, leveraging genetic variants as instrumental variables to deduce causal relationships between risk factors and disease manifestations, circumventing confounding factors and reverse causation.…”

Section: Introductionmentioning

confidence: 99%

Exploring causal correlations between inflammatory cytokines and varicose veins: A Mendelian randomization analysis

Min,

Xing,

Jiang

et al. 2024

International Wound Journal

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This study aimed to investigate the causal relationship between inflammatory cytokines and the risk of varicose veins. The data were sourced from genome‐wide association studies (GWAS) of European individuals. Multiple Mendelian randomization (MR) methods were used to evaluate the association between inflammatory cytokines and varicose veins. The study found significant associations between elevated levels of certain inflammatory biomarkers (e.g., CASP‐8, Vascular endothelial growth factor A levels (VEGF_A)) and an increased risk of varicose veins, while others (e.g., 4EBP1, MMP‐10) showed a protective effect. The MR‐Egger Intercept and heterogeneity tests indicated no significant pleiotropy or heterogeneity. This comprehensive MR analysis identifies several cytokines as potential contributors to the pathogenesis of varicose veins, offering insights into novel therapeutic targets. Our findings underscore the importance of inflammation in varicose veins and suggest that targeting specific cytokines could be a promising strategy for the treatment and prevention of varicose veins.

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Cytokines and Venous Leg Ulcer Healing—A Systematic Review

Cited by 24 publications

References 99 publications

Evaluation of factors affecting the healing process of venous ulcers: A 12‐week longitudinal study

Evaluation of factors affecting the healing process of venous ulcers: A 12‐week longitudinal study

Boosting UPR transcriptional activator XBP1 accelerates acute wound healing

Exploring causal correlations between inflammatory cytokines and varicose veins: A Mendelian randomization analysis

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