Correlation of TNF-α, Cys C, and NLRP3 inflammasomes with venous ulcers in patients with lower extremity varicose veins

Am J Transl Res. 2023 Feb 15;15(2):1186-1194. eCollection 2023.

Abstract

Objective: To explore the correlation of tumor necrosis factor α (TNF-α), cystatin C (Cys C), and NLR family pyrin domain containing 3 (NLRP3) inflammasomes with venous ulcers from lower extremity varicose veins.

Methods: In this retrospective analysis, 135 patients with primary varicose veins of lower extremities were selected and divided into a varicose ulcer group (n=32) and a non-varicose ulcer group (n=103) according to clinical ulcer presence. Healthy adults with similar general information during the same period were included as a healthy controls (n=30). The levels of TNF-α, interleukin-1β (IL-1β), Cys C, and NLRP3 inflammasomes were statistically analyzed among the three groups. Logistic regression was used for analyzing the risk factors for venous ulcers in patients with varicose veins of the lower extremities. Spearman correlation was applied for correlation analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was found to disclose the predictive value of TNF-α, Cys C, and NLRP3 inflammasomes for venous ulcers.

Results: (1) Logistic regression analysis showed that TNF-α, IL-1β, and NLRP3 inflammasomes were risk factors for venous ulcers in patients with varicose veins of the lower extremity, and Cys C in ulcer wound tissue was a protective factor. (2) TNF-α was significantly correlated with IL-1β and Cys C in ulcer wound tissue, and NLRP3 in plasma (r=0.256, -0.290, 0.305; P=0.003, 0.001, <0.001). IL-1β was significantly correlated with CysC in ulcer wound tissue and plasma (r=-0.251, -0.193; P=0.003, 0.025). (3) The AUC, sensitivity, and specificity of TNF-α and NLRP3 inflammasomes for predicting varicose veins were high, with AUC of 0.881 and 0.712, sensitivity of 0.875% and 0.875%, and specificity of 0.893% and 0.738%, respectively.

Conclusion: TNF-α in plasma, Cys C in ulcer wound tissue and plasma, and NLRP3 inflammasomes in plasma were closely related to the occurrence of venous ulcers in patients with varicose veins of the lower and may serve as new targets for treatment.

Keywords: Cys C; NLRP3 inflammasome; TNF-α; correlation; varicose veins of lower extremity; venous ulcer.