Abstract
Varicose veins are a disease with high incidence and prevalence. In the venous wall, the smooth muscle cells (SMCs) act in the vascular homeostasis that secretes multiple substances in response to stimuli. Any alteration of these cells can modify the function and structure of the other venous layers such as the endothelium, resulting in increases in endothelial permeability and release of substances. Therefore, knowing the cellular and molecular mechanisms of varicose veins is imperative. The aims of this study are to understand how SMCs of patients with varicose veins subjected to saphenectomy of the great saphenous vein react under hypoxic cell conditions and to determine the role of vascular endothelial growth factor (VEGF) in this process. We obtained SMCs from human saphenous vein segments from patients with varicose veins (n=10) and from organ donors (n=6) undergoing surgery. Once expanded, the cells were subjected to hypoxic conditions in specific chambers, and expansion was examined through analyzing morphology and the expression of α-actin. Further gene expression studies of HIF-1α, EGLN3, VEGF, TGF-β1, eNOS, and Tie-2 were performed using RT-qPCR. This study reveals the reaction of venous cells to sustained hypoxia. As significant differential gene expression was observed, we were able to determine how venous cells are sensitive to hypoxia. We hypothesize that venous insufficiency leads to cellular hypoxia with homeostatic imbalance. VEGF plays a differential role that can be related to the cellular quiescence markers in varicose veins, which are possible therapeutic targets. Our results show how SMCs are sensitive to hypoxia with a different gene expression. Therefore, we can assume that the condition of venous insufficiency leads to a situation of sustained cellular hypoxia. This situation may explain the cellular response that occurs in the venous wall as a compensatory mechanism.
Highlights
Chronic venous disease refers to morphological and functional anomalies of the venous system and includes a series of clinical manifestations of varying severity of which varicose veins (VV) are the most common [1, 2]
The important role of vascular endothelial growth factor (VEGF) in vascular pathology has been highlighted by numerous authors, with studies mentioning its role in angiogenesis and cell signaling [25, 26]
In the controls, the expression of VEGF is significantly higher under hypoxic conditions compared to normoxic conditions
Summary
Chronic venous disease refers to morphological and functional anomalies of the venous system and includes a series of clinical manifestations of varying severity of which varicose veins (VV) are the most common [1, 2]. Within this pathology, family history, aging, hormones, obesity, and pregnancy are the most important risk factors [3,4,5]. Any alteration of these cells can modify the function and structure of the other venous layers, resulting in the appearance of phenomena such as thrombosis, increased endothelial permeability with edema, and toxic substance release, which can lead to inflammation, ischemia, and even cell necrosis [10, 14]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have