Programmed cell death (apoptosis) and its role in the pathogenesis of lower extremity varicose veins

The etiology of varicose veins remains elusive. We hypothesized that abnorm al cell cycle events in the vein wall may contribute to changes in its stru ctural integrity predisposing to varicosity development. Since cell cycle c heckpoint controls are linked to the signaling and execution of apoptotic c ascades, possibly apoptosis is a contributing factor in the pathophysiology of varicosities. The present study was designed to investigate whether pro grammed cell death varies in varicosities as compared to normal veins. Twen ty-seven normal greater saphenous vein specimens were obtained from patient s undergoing infrainguinal arterial bypass surgery, and 20 varicose vein sp ecimens were retrieved from patients undergoing varicose vein excision. Apo ptosis was detected by TUNEL assay. Expression of bcl-2 and cyclin D1 was n oted by standard immunohistochemical techniques. Apoptotic cells were ident ified in 32 of the 47 specimens. Forty-eight percent of normal vein specime ns displayed >3 apoptotic cells per 100 cells in the adventitia; 15% of the specimens of the varicose vein group showed such magnitude of apoptosis (p < 0.03). This increased apoptotic activity was not observed in media or in tima of either vein group (p < 0.001). No significant difference in immunor eactivity to bcl-2 protein was observed in varicose vein specimens as compa red to controls. Varicose vein specimens demonstrated increased nuclear exp ression of cyclin D1 whereas its cytoplasmic expression was significantly d iminished (p less than or equal to 0.02). These data show that programmed c ell death is inhibited in varicose veins. Differential expression of cyclin D1 suggests that it may deregulate cell cycle events, thereby leading to v aricosity formation. DOI: 10.1007/s100169910005.