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Role of mechanosignaling on pathology of varicose vein

Abstract

Varicose veins are the most common vascular disease in humans. Veins have valves that help the blood return gradually to the heart without leaking blood. When these valves become weak, blood and fluid collect and pool by pressing against the walls of the veins, causing varicose veins. In the cardiovascular system, mechanical forces are important determinants of vascular homeostasis and pathological processes. Blood vessels are constantly exposed to a variety of hemodynamic forces, including shear stress and environmental strains caused by the blood flow. In varicose veins within the leg, venous blood pressure rises in the vein of the lower extremities due to prolonged standing, creating a peripheral tension in the vessel wall thereby causing mechanical stimulation of endothelial cells and vascular smooth muscle. Studies have shown that long-term increased exposure to vascular wall tension is associated with the overexpression of HIF-1α and HIF-2α and increased levels of MMP-2 and MMP-9, thereby reducing venous contraction and progressive venous dilatation, which is involved in the development of varicose veins. Following the expression of metalloproteinase, the expression of type 1 collagen increases, and the amount of type 3 collagen decreases. Therefore, collagen imbalance will cause the varicose veins to not stretch. Loss of structural proteins (type 3 collagen and elastin) in the vessel wall causes the loss of the biophysical properties of the varicose vein wall. This review article tries to elaborate on the effect of mechanical forces and sensors of these forces on the vascular wall in creating the mechanism of mechanosignaling, as well as the role of the onset of molecular signaling cascades in the pathology of varicose veins.

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Fig. 1

Abbreviations

MMP:

Matrix metallopeptidases

HIF:

Hypoxia-inducible factor-1alpha

FOXC2:

Forkhead box protein C2

MTHFR:

Methylene tetrahydrofolate reductase

CSK:

C-terminal Src kinase

ROS:

Reactive oxygen species

eNOS:

Endothelial NOS

ECM:

Extracellular matrix

RGD:

Arg-Gly-Asp

LOXL1:

Lysyl oxidase-like 1

VEGF:

Vascular endothelial growth factor

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Correspondence to Shirin Saberianpour.

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Saberianpour, S., modaghegh, M.H.S., Rahimi, H. et al. Role of mechanosignaling on pathology of varicose vein. Biophys Rev 13, 139–145 (2021). https://doi.org/10.1007/s12551-021-00783-z

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  • DOI: https://doi.org/10.1007/s12551-021-00783-z

Keywords

  • Varicose
  • Veins
  • Mechanosignaling