Endolhelial injury is a major manifestation of septic shock induced by lipopolysaccharide (LPS). Recently, LPS was shown to induce apoptosis in human microvascular endothelial cells via caspase activation. In this study, we have further defined the apoptolic pathway induced by LPS in human umbilical vein endothelial cells (HUVEC). We found that LPS treatment increased caspase-3 activity and augmented expression of the pro-apoptotic protein Bax and the tumor suppressor gene p53. LPSinduced expression of these pro-apoptotic molecules occurred concurrently with decreased expression of the pro-survival protein, Bcl-2. The pro-apoptotic Bax protein was found to translocate to the mitochondria from the cytosol following stimulation with LPS. Vascular endothelial growth factor (VEGF), a known cell survival factor, blocked LPSinduced apoptosis. Pretreatment of HUVEC with VEGF inhibited the expression of both Bax and p53. VEGF also sustained the expression of Bcl-2 following LPS treatment. These data suggest that VEGF could act to protect endothelium from LPS-mediated apoptosis by inhibiting induction of downstream pro-apoptotic molecules.
|Issue number||11 PART I|
|State||Published - 1 Dec 2000|