Transforming growth factor-β1 and inducible nitric oxide synthase signaling were involved in effects of prostaglandin E2 on progression of lower limb varicose veins

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ObjectiveThe vital pathogenesis of varicose veins includes remodeling of the extracellular matrix and decreased vascular tone. Prostaglandin E2 (PGE2), 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 PGE2 in the development of varicose veins in lower limbs. MethodsThe collected venous specimens were analyzed using hematoxylin and eosin, Masson's trichrome, and immunohistochemical staining. Transforming growth factor (TGF)-β1, PGE2, CD31, and α-smooth muscle actin antibody were used to detect the expression and distribution of these proteins. The effect of PGE2 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 PGE2 and matrix metalloproteinases (MMPs) was assessed using Western blotting. Quantitative reverse transcription polymerase chain reaction was used to evaluate the effect of PGE2 on the expression of nitric oxide synthase (NOS) and other genes. ResultsThe expression of PGE2 and TGF-β1 in varicose veins was upregulated in the media tunica and intima tunica, and a strong positive correlation was found between PGE2 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). PGE2 promoted the migration and tube formation ability of HUVECs. Moreover, PGE2 also upregulated the expression of MMP-1 and TGF-β1 in HUVECs and increased the mRNA level of inducible NOS. ConclusionsPGE2 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. PGE2 can also reduce the tension of the great saphenous vein by promoting the expression of inducible NOS, thus aggravating the blood stasis.