Protection against necrosis but not apoptosis by heat-stress proteins in vascular smooth muscle cells evidence for distinct modes of cell death

We have reported previously that cultured vascular smooth muscle cells (VSM C) isolated from spontaneously hypertensive rats (SHR) show higher prolifer ation and cell death than normotensive controls. In addition to protecting cells against death, heat stress proteins (HSPs) appear to play a role in c ell proliferation. This investigation examines the involvement of HSP72 and HSP27 in altered SHR VSMC proliferation and death. We have performed detai led discriminatory analysis to characterize which type of VSMC death is ind uced by heat stress (HS) and serum deprivation, Serum deprivation induced a poptosis (caspase-3 cleavage and DNA laddering) and secondary necrosis, the 2 processes being a continuum of each other. Ln contrast, acute HS (46 deg rees C, 30 minutes), which inhibited BN.lx and SHR VSMC proliferation by 2- fold, increased necrosis (by 5-fold and 2-fold, respectively) but not apopt osis. HSP72 and HSP27 expression evoked in VSMC by mild HS (44 degrees C, 1 5 minutes) 6 hours before acute HS prevented the inhibition of proliferatio n and induction of necrosis with no effect on serum deprivation-induced or staurosporine-induced apoptosis. This induced expression of HSP72 and HSP27 did not eliminate the higher basal proliferation, apoptosis, and necrosis of SHR VSMC compared with BN.lx VSMC, suggesting that these HSPs are not in volved in altered SHR VSMC proliferation and death. Also, although apoptosi s and necrosis may he a continuum, in VSMC the 2 processes may be distingui shed by HS, in which only necrosis is prevented by prior HSP accumulation T his observation may be of use in designing strategies for cellular protecti on.