Intense remodeling of extracellular matrix within the varicose vein: the role of gelatinases and vascular endothelial growth factor

Abstract

Background Increased blood pressure in the varicose veins (VV) can contribute to the overexpression of matrix metalloproteinases (MMPs), affecting the endothelium, smooth muscle, and extracellular matrix of the vein wall. Gelatinases (MMP-2 and MMP-9), hypoxia, and inflammation occurring in the VV wall contribute to the increased expression of vascular endothelial growth factor (VEGF). Aims Our objective was to analyze the concentration of gelatinases and VEGF in the great saphenous VV wall and plasma of patients. Methods In total, 65 patients (2nd degree according to clinical state classification, etiology, anatomy, and pathophysiology—CEAP classification) aged 22 to 70 were enrolled. Control veins (n = 10) were collected from the patients who underwent coronary artery bypass graft surgery. Control plasma (n = 20) was obtained from healthy individuals. Gelatinases and VEGF levels were measured with the usage of ELISA method. Results A significant increase in MMP-9 (11.2 vs. 9.98 ng/mg of protein) and VEGF (41.06 vs. 26 ng/g of protein) concentration in VV wall compared with control veins was observed. A positive correlation between VEGF versus MMP-2 (p = 0.03, r = 0.27) was found in the VV wall. However, no correlation was found between the concentration of VEGF and MMP-9 (p = 0.4, r = 0.11) in the VV wall. In addition, no statistical differences between MMP-9, MMP-2, and VEGF levels in plasma of VV patients compared with controls were noticed. Conclusions The results of the present study confirm that VV’s patients have altered expression of MMPs and VEGF. Overexpression of MMP-9 and VEGF in the VV wall may contribute to the spreading of inflammatory process and suggests the intense remodeling of extracellular tissue within the VV wall.

Potential Molecular Mechanism of Guishen Huoxue Decoction against Intrauterine Adhesion Based on Network Pharmacology

“…VEGF is the major inducer of angiogenesis in a variety of in vivo models and plays an essential role in numerous physiological and Evidence-Based Complementary and Alternative Medicine pathological processes, including angiogenesis and immune response [26,27]. Increased expression of VEGF has been reported to alleviate endometrium injury in a wounded rat uterus [28]. e patients with IUA showed vascular closure in endometrial tissues and had significantly increased VEGF expression after therapy, suggesting angiogenesis in the endometrial tissues may affect the endometrial repair [29].…”

Understanding Chronic Venous Disease: A Critical Overview of Its Pathophysiology and Medical Management

“…It is known that the regulation of voltage dependent Ca 2+ channels is altered with aging processes and hence affects vascular function [ 218 ]. Furthermore, some studies reported that primary VV show aberrant release of VEGF, which, in combination with other altered molecules, might increase the permeability of venous wall, allowing the infiltration of inflammation markers [ 219 ].…”

Verständnis, Prävention und Behandlung von venösen und lymphatischen Erkrankungen basieren auf der Arbeit von Grundlagenforschern

“…In Varizen wurden MMP-1, -2, -3, -7, -9 und -13 untersucht. In Varizen wurde eine Überexpression von MMP-9 im Zusammenhang mit einem erhöhten Gehalt an vaskulärem endothelialem Wachstumsfaktor (VEGF) festgestellt [10]. VEGF ist ein Molekül (Wachstumsfaktor), das von verschiedenen Zellen produziert wird (Thrombozyten, Makrophagen, Mesangiumzellen der Niere usw.…”

“…MMP-1, -2, -3, -7, -9 and -13 have been studied in varicose veins. Overexpression of MMP-9 was found in varicose veins, with a positive correlation with elevated levels of vascular endothelial growth factor (VEGF) [10]. VEGF is a molecule (a grow factor) produced by several cells (platelets, macrophages, renal mesangial cells, etc.)…”