Associations of NF-kappaB and Bax with Apoptosis in Varicose Veins of Women of Different Age Groups

Helle Evi Simovart,Andres Arend,Jüri Lieberg,Marina Aunapuu

doi:10.1155/2011/639720

Helle Evi Simovart, Andres Arend + Show 2 more

Open Access

https://doi.org/10.1155/2011/639720

Copy DOI

Abstract

The study aimed at detecting apoptotic endothelial cells (ECs) and smooth muscle cells (SMCs) together with determining expression of NF-kappaB (p105/p50) and Bax in varicose vein walls. Women (n = 35) undergoing the excision of varicose veins were divided into 3 groups: younger than 35 years (I), 36–50 years (II), and older than 50 years (III). Apoptosis was determined by the TUNEL method, NF-kappaB and Bax expression by immunohistochemistry. The percentage of apoptotic ECs and SMCs in the layers of varicose vein wall increased in groups II and III. NF-kappaB expression had the lowest level in Group II with particularly low level in the media. Contrariwise, Bax expression levels in Group II were increased. The study revealed that in varicose veins ECs and SMCs apoptosis increased with advancing age. If increase in apoptosis during earlier stages of varicosities is probably regulated by intrinsic pathway, then in older patients other signaling pathways may be involved.

Highlights

Varicose veins of legs are one of the commonest diseases affecting people worldwide
The intrinsic pathway of apoptosis occurs as a consequence of mitochondrial permeabilization and is regulated by proapoptotic proteins such as Bcl-2-associated protein x (Bax), and it involves specific caspases, especially caspase 9 [16]
Bax is a protein that forms a homodimer or heterodimers with Bcl-2, and apoptosis depends on the ratio of these two proteins because it is promoted by Bax and inhibited by Bax/Bcl-2 heterodimers [17]

Summary

Introduction

Despite extensive studies, the etiology of varicose veins is still unclear as well as molecular mechanisms that could potentially lead to the dilation of the vein wall. Dysfunctional endothelial cells (ECs) and smooth muscle cells (SMCs) are probably the crucial regulators in the cascade of events leading to the restructuring of the vein wall with consequent venous dilatation. The endothelium regulates venous tone through release of vasoactive substances constricting and relaxing the veins. Both reduction of factors contributing to vasoconstriction and upregulation of factors contributing to vasodilatation have been shown in varicose veins [2,3,4]. As reported by Wali and Eid [6, 7], damaged

Methods

Results

Discussion

Conclusion