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 abnormal cell cycle events in the vein wall may contribute to changes in its structural integrity predisposing to varicosity development. Since cell cycle checkpoint controls are linked to the signaling and execution of apoptotic cascades, possibly apoptosis is a contributing factor in the pathophysiology of varicosities. The present study was designed to investigate whether programmed cell death varies in varicosities as compared to normal veins. Twenty-seven normal greater saphenous vein specimens were obtained from patients undergoing infrainguinal arterial bypass surgery, and 20 varicose vein specimens were retrieved from patients undergoing varicose vein excision. Apoptosis was detected by TUNEL assay. Expression of bcl-2 and cyclin D1 was noted by standard immunohistochemical techniques. Apoptotic cells were identified in 32 of the 47 specimens. Forty-eight percent of normal vein specimens 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 intima of either vein group (p < 0.001). No significant difference in immunoreactivity to bcl-2 protein was observed in varicose vein specimens as compared to controls. Varicose vein specimens demonstrated increased nuclear expression of cyclin D1 whereas its cytoplasmic expression was significantly diminished (p </=0.02). These data show that programmed cell death is inhibited in varicose veins. Differential expression of cyclin D1 suggests that it may deregulate cell cycle events, thereby leading to varicosity formation.
Ascher
E
E
Division of Vascular Surgery, Maimonides Medical Center, Brooklyn, NY 11219, USA.
Jacob
T
T
Hingorani
A
A
Gunduz
Y
Y
Mazzariol
F
F
Kallakuri
S
S
D017209:Apoptosis; D002453:Cell Cycle; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014648:Varicose Veins / Q000473:pathology / Q000503:physiopathology*
D019253:Proto-Oncogene Proteins c-bcl-2; D019938:Cyclin D1