Smooth Muscle Cell Apoptosis in Primary Varicose Veins

Abstract

Objectives One of the important factors responsible for vessel wall remodelling is programmed cell death. In the paper the role of smooth muscle cell (SMC) apoptosis in primary varicose veins (PVV) is investigated. Material and methods Vein specimens were obtained from 40 patients with PVV. In each case proximal and distal (upper crural) great saphenous veins (GSV) were harvested. Morphometric computer assessed quantitative evaluation of SMCs, collagen and elastin content was carried out. Apoptotic cells were detected by TUNEL assay. The levels of p53, BAX, BCLl-2 and p21 mRNA expression were assessed by real time RT-QPCR and the presence of respective proteins in the vessel wall was confirmed by immunohistochemistry. Results In the proximal GSV segments a significant increase of p53, p21 and BCL-2 mRNA levels was found in PVV patients. In the distal segments BAX and BCL-2 expression levels were higher. Taking into account the patient age, elevated p53 mRNA expression level was noticed in the distal incompetent GSVs of young PVV patients. In this group a statistically significant increase in the apoptotic index (APIx) within the vein media was found which correlated positively with p53 mRNA expression level. There was no increase of the apoptotic activity in elderly patients that led to the structural changes increase. In proximal GSV segments, despite SMC amount reduction or presence of structural changes in perivalvular wall region, no increase of the APIx with was noticed. Conclusions P53—related apoptosis is one of the regulatory mechanisms of vein wall homeostasis maintenance. During varicose vein development its activation is related to the early stages of the disease. In the further course, the down-regulation of the SMC apoptosis within the vein media leads to the structural changes increase. The reduction of the SMC population corresponding to an increase of p21 expression in proximal saphenous vein segments suggests that the cell cycle disturbances may lead to the ‘weakness’ of the proximal GSV wall. Valve injury is not the only factor leading to the varicose veins occurrence.