Transforming growth factor-β1 and inducible nitric oxide synthase signaling were involved in effects of prostaglandin E 2 on progression of lower limb varicose veins.

Objective: The vital pathogenesis of varicose veins includes remodeling of the extracellular matrix and decreased vascular tone. Prostaglandin E ₂ (PGE ₂ ), a small molecule substance and inflammatory medium that belongs to the arachidonic acid derivatives, has the capacity to influence the expression of metalloproteinase and the vascular tone of the venous wall. The purpose of the present study was to investigate the role of PGE ₂ in the development of varicose veins in lower limbs.
Methods: The collected venous specimens were analyzed using hematoxylin and eosin, Masson's trichrome, and immunohistochemical staining. Transforming growth factor (TGF)-β1, PGE ₂ , CD31, and α-smooth muscle actin antibody were used to detect the expression and distribution of these proteins. The effect of PGE ₂ on the proliferation, migration, and tube formation capacity of human umbilical vein endothelial cells (HUVECs) was detected in vitro. The effect of TGF-β1 on the expression of PGE ₂ and matrix metalloproteinases (MMPs) was assessed using Western blotting. Quantitative reverse transcription polymerase chain reaction was used to evaluate the effect of PGE ₂ on the expression of nitric oxide synthase (NOS) and other genes.
Results: The expression of PGE ₂ and TGF-β1 in varicose veins was upregulated in the media tunica and intima tunica, and a strong positive correlation was found between PGE ₂ and TGF-β1 expression in both varicose veins (95% confidence interval, 0.5207-0.9582; R = 0.848; P = .0005) and normal veins (95% confidence interval, 0.2530-0.8532; R = 0.643; P = .003). PGE ₂ promoted the migration and tube formation ability of HUVECs. Moreover, PGE ₂ also upregulated the expression of MMP-1 and TGF-β1 in HUVECs and increased the mRNA level of inducible NOS.
Conclusions: PGE ₂ can affect the remodeling of the extracellular matrix and reduce the elasticity of the vascular walls by promoting the synthesis of TGF-β1 and MMP-1. PGE ₂ can also reduce the tension of the great saphenous vein by promoting the expression of inducible NOS, thus aggravating the blood stasis.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)