Mutual exclusion of apoptosis and hsp70 in human vein intimal hyperplasia in vitro

Background. Apoptosis of vascular smooth muscle cells (VSMC) plays a role i n physiological vascular remodeling, as well as in disease states such as a therosclerosis and restenosis after angioplasty. Heat shock protein 70 (hsp 70) may protect the cell against apoptosis and/or necrosis. In this study, we examined hsp70 expression and its temporal relationship to cell survival or death in a model of intimal vein hyperplasia in vitro. Methods. Segments of human saphenous veins were placed into culture. At dif ferent days vein segments were serum-starved or exposed to heat shock. Apop tosis and hsp70 expression were analyzed by Western blot, immunohistochemis try, and TUNEL assay, Results. A marked intimal vein hyperplasia developed after 14 days of cultu re when compared with baseline. hsp70 was present at baseline and disappear ed during culture. Heating during culture could not up-regulate hsp70. The apoptotic markers were absent at baseline and present during normal culture , Conversely, serum starvation stimulated strong hsp70 expression coinciden tal with the disappearance of apoptotic markers. Conclusions. Stimulation of veins during culture with serum resulted in hyp erplasia, apoptosis, and inhibition of hsp70 expression. Down-regulation of hsp70 may permit apoptosis and vessel wall remodeling in this model. (C) 2 001 Academic Press.