Abstract
Lower extremity varicose veins are a common condition in vascular surgery and proliferation of vascular smooth muscle cells (VSMCs) in the intima is a significant pathological feature of varicosity. However, the pathogenesis of varicose veins is not fully understood. Osteopontin (OPN) could promote the migration and adhesion of VSMCs through the cell surface receptor integrin β3 and the cooperation of OPN and integrin β3 is involved in many vascular diseases. However, the role of OPN and integrin β3 in varicosity remains unclear. In the current study, we found that the methylation levels in the promoter regions of OPN and integrin β3 genes in the VSMCs of varicose veins are reduced and the protein expression of OPN and integrin β3 are increased, compared with normal veins. Furthermore, it was observed that VSMCs in the neointima of varicose veins were transformed into the synthetic phenotype. Collectively, hypomethylation of the promoter regions for OPN and integrin β3 genes may increase the expression of these genes in varicosity, which is closely related to VSMC phenotype switching. Hypomethylation of the promoter regions for OPN and integrin β3 genes may be a key factor in the pathogenesis of varicosity.
Highlights
Lower extremity venous insufficiency is a common condition in vascular surgery, with approximately25% of the population having lower extremity varicose veins [1]
There are a number of longitudinally oriented vascular smooth muscle cells (VSMCs) in the neointima of varicose veins
Consistent with the study of Thyberg et al [24], our results suggest that the VSMC in the neointima of varicose vein have the characteristics of synthetic phenotype
Summary
Lower extremity venous insufficiency is a common condition in vascular surgery, with approximately. 25% of the population having lower extremity varicose veins [1]. Most of these are varicosis of the great saphenous vein. Vascular remodeling is closely related to changes in gene expression, physical and chemical vascular damage and stimulation of metabolic and vasoactive substances [2,3]. Proliferation of vascular smooth muscle cells (VSMCs) in the intima is a significant pathological feature of varicosity [4]. Phenotype switching of VSMCs is the cytological basis for vascular remodeling. VSMCs exhibit a phenotypic change characterized by loss of contractility and abnormal proliferation, migration and matrix secretion
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