Apoptosis Of Vein Endothelial Cells Research Articles

P-251 The Antioxidant Effects of Quercetin Metabolites on Prevention of High Glucose-Induced Apoptosis of Human Umbilical Vein Endothelial Cells

P-251 The Antioxidant Effects of Quercetin Metabolites on Prevention of High Glucose-Induced Apoptosis of Human Umbilical Vein Endothelial Cells

Mechanism underlying the protective effects of glutaredoxin-1 against high glucose-induced apoptosis of umbilical vein endothelial cells

Mechanism underlying the protective effects of glutaredoxin-1 against high glucose-induced apoptosis of umbilical vein endothelial cells

Proteinase-activated receptor-1 mediates allogeneic CD8+ T cell-induced apoptosis of vascular endothelial cells

Vascular endothelial-cells injury plays a pivotal role in the pathogenesis of graft-versus-host disease (GVHD) and transplant-associated endothelial injury syndrome. Vascular endothelial cells are an exposed target tissue for immune-mediated injury during GVHD. Early endothelial injury syndromes share common features with acute GVHD. Chronic GVHD leads to a rarefaction of microvessels caused by the infiltration of alloreactive cytotoxic T lymphocytes. In this context, allogeneic reactive cytotoxic T cell may contribute to apoptosis of vascular endothelial cells. The involvement of proteinase-activated receptor (PAR-1) in regulation of apoptosis has been recently recognized in many cell types. We hypothesized that apoptosis of vascular endothelial cells induced by allogeneic cytotoxic T cell are mediated via the PAR-1. Allogeneic CD8(+) T cell, PAR-1 agonist peptide (SFLLRN) induced apoptosis of human umbilical vein endothelial cells (HUVECs) and human dermal microvascular endothelial cells (HDMECs) as assessed by AnnexinV-FITC labeling. To ascertain the mechanism of endothelial apoptosis, we determined that allogeneic CD8(+) T cell, SFLLRN enhanced cleavage of caspase-3 and led to p38MAPK activation as assessed by Western blot. The effects of allogeneic CD8(+) T cell and SFLLRN on apoptosis of vascular endothelial cells were largely prevented by a cleavage-blocking anti-human PAR-1-antibody (ATAP2) and a specific inhibitor of p38MAPK. In concert, these observations provide strong evidence that allogeneic CD8(+) T cell induces apoptosis of human vascular endothelial cells through PAR-1-dependent modulation of intrinsic apoptotic pathway via alterations of p38MAPK and caspase-3.

Abstract 5508: PSGL-1-expressing CD4 T Cells Induce Endothelial Injury in Perimenopausal Women with Low Estrogen Levels

Background: Atherosclerosis develops rapidly in postmenopausal women, and plaque erosion induces acute coronary syndromes (ACS) in perimenopausal women (PMW). However, the causal relationship between low estrogen levels and the mechanism of plaque erosion in PMW is not fully resolved. We examined whether PWM have historical T cell dysfunction related to adhesion molecules, and whether they experience accelerated plaque erosion as a result. Methods and Results: Fresh CD4 T cells were isolated from 62 PMW (mean age 54.0±5.0 years) and 69 women with regular menstruation cycles (NC, mean age 33.0±8.0 years). Estrogen levels were lower in PMW than in NC (P<0.0001). Measurements of DAPI-binding nuclear protein fragmentations showed that CD4 T cells from PMW induced significant human umbilical vein endothelial cells (HUVEC) apoptosis compared to CD4 T cells from NC (P<0.002). Furthermore, CD4 T cells from PMW had high T cell activation marker CD69 (P<0.001) and expressed strong p-selectin glycoprotein ligand-1(PSGL-1) and integrinβ 2 but not L-selectin and integrin α M by FACS (P<0.0001, P<0.04, respectively). Estrogen levels correlated negatively with PSGL-1 (R=0.448, P<0.02) and integrinβ 2 (R=0.442, P<0.03), and negatively with CD4 T cell-induced HUVEC apoptosis (R=0.524, P<0.03). Rolling and adhesion of CD4 T cells to activated HUVEC under laminar flow showed strong correlation with HUVEC apoptosis (R=0.717, P<0.03 and R=0.562, P<0.03, respectively). Anti-PSGL-1 Ab inhibited both CD4 T cell-rolling and CD4 T cell-adhesion to activated HUVEC (P<0.05, P<0.009, respectively), but anti-CD18 Ab only affected cell-adhesion (P<0.006). Finally, we included anti-PSGL-1 Ab and anti-CD18 Ab in the apoptosis assay due to investigate whether the CD4 T cell-mediated apoptosis of endothelial cells was dependent on PSGL-1. Anti PSGL-1Ab treatment reduced CD4 T cell-induced apoptosis of endothelial cells (P=0.001) while anti integlinβ 2 Ab did not. Conclusions: From these results, we concluded that PSGL-1-expressing CD4 T cells in PMW with low estrogen levels is a factor that contributes to the acceleration of atherosclerosis and plaque erosion.

Docetaxel-induced apoptosis of human umbilical vein endothelial cells (HUVECs) is mediated by the activation of MAPK and modulation in Bcl-2 family proteins

Docetaxel-induced apoptosis of human umbilical vein endothelial cells (HUVECs) is mediated by the activation of MAPK and modulation in Bcl-2 family proteins

Nerve growth factor promotes formation of lumen-like structures in vitro through inducing apoptosis in human umbilical vein endothelial cells

Recent evidence suggests that apoptosis of endothelial cells contributes to lumen formation during angiogenesis, but the biological mechanism remains obscure. In this study, we investigated the effect of nerve growth factor (NGF), a member of the neurotrophin family and a potential angiogenic factor, on human umbilical vein endothelial cells (HUVEC) apoptosis and the formation of lumen-like structures (LLS) by cultured HUVEC on Matrigel. We demonstrate that NGF induces cell apoptosis. NGF treatment has no significant effect on the expression level of its two receptors, TrkA and p75NTR. Blockade of both TrkA and p75NTR, but not that of either receptor alone significantly decreases NGF-induced cell apoptosis. NGF significantly increases formation of LLS which consist substantially of apoptotic cells. Application of NGF-neutralizing antibody or simultaneous blockade of TrkA and p75NTR significantly blocks spontaneous and NGF-induced LLS formation. These data support a role for NGF-induced cell apoptosis in LLS formation in vitro.

Abstract 130: CD4 T Cell Dysfunction Induced to Endothelial Apoptosis in Peri-menopausal Women with Low Estrogen levels

Background : Plaque erosion is responsible for the majority of acute coronary thrombi and induces acute coronary syndromes (ACS) in perimenopausal women. However, the causal relationship between low estrogen levels and plaque erosion mechanism in perimenopausal women is not fully understood. We examined whether perimenopausal women (PMW) with low levels of estrogen have had T cell dysfunction, and whether they experienced accelerated plaque erosion as a result. Methods and Results : Fresh CD4 T cells were isolated from 45 PMW within 5 years after menopause (mean age 53.9 ± 6.0 years) and 40 women with regular menstruation cycles (NC, mean age 34.0 ± 7.4 years). Estrogen levels in plasma were lower in PMW than NC (P < 0.0001). Estrogen receptor α (ESR1) and estrogen receptor β (ESR2) mRNA of CD4 T cells in PMW were lower compared to NC by real time PCR (P < 0.05). Estrogen levels correlated significantly with ESR1 transcripts (R = 0.537, P < 0.03). The inflammation marker of hsCRP was higher (P < 0.003) and CD69, an activation marker of T cells, had stronger expression on CD4 T cells from PMW by FACS (P < 0.04). Measurement of fragmentation of DAPI-binding nuclear proteins showed that CD4 T cells from PMW induce significant human umbilical vein endothelial cells (HUVEC) apoptosis compared to those from NC (P < 0.001). Furthermore, CD4 T cells from PMW expressed strong p-selectin glycoprotein ligand-1(PSGL-1) and integrin (CD18) but not L-selectin by FACS (P < 0.006, P < 0.05, n.s., respectively). Estrogen levels correlated negatively with PSGL-1 (R = 0.997, P < 0.05) and CD4 T cell-induced HUVEC apoptosis (R = 0.439, P < 0.0001). Treatment with 17β-estradiol showed reduction of CD4 T cell-induced apoptosis in PMW. Estrogen receptor antagonist ICI 172,780 abolished estrogen protection. Conclusions : From these results, we concluded that CD4 T cells in perimenopausal women were already activated and displayed dysfunctions related to deficiency of estrogen and estrogen receptors, which may be a factor that contributes to the acceleration of plaque erosion in atherosclerotic plaque and acute coronary syndromes.

Abstract 1201: Lack of Dehydroepiandrosterone-sulfate (DHEAS) contributes to CD4 T Cell-Induced Endothelial Apoptosis in Perimenopausal Women

Background: Postmenopausal women develop atherosclerosis faster and have higher incidence of acute coronary syndromes. Endogenous dehydroepiandrosterone-sulfate (DHEAS) is a major source of estrogen for women after menopause. Low levels of DHEAS is also a known risk factor for coronary atherosclerotic disease in men. However, the causal relationship between DHEAS levels in women and acute coronary syndromes (ACS) is not fully understood. In this study, we examined whether CD4 T cells from perimenopausal women (PMW) with low levels of DHEAS induce endothelial apoptosis that is prone to develop plaque erosion. Methods and Results: Fresh CD4 T cells were isolated from 45 PMW within 5 years after menopause (mean age 53.9 ± 6.0 years) and from 40 women with regular menstruation cycles (NC, mean age 34.0 ± 7.4 years). DHEAS levels in plasma by ELISA correlated negatively with age (R = 0.500, P < 0.02). DHEAS was lower in PMW than in NC (P < 0.0001). Estrogen receptor α (ESR1) and estrogen receptor β (ESR2) mRNA of CD4 T cells in PMW were lower compared to NC by real time PCR (P < 0.05). DHEAS levels correlated significantly with ESR2 transcripts (R = 0.789, P < 0.0001), but not with ESR1. Measurement of fragmentation of DAPI-binding nuclear proteins showed that CD4 T cells from PMW induce significant human umbilical vein endothelial cells (HUVEC) apoptosis compared to those from NC (P<0.0001). DHEAS levels correlated negatively with CD4 T cell-induced HUVEC apoptosis (R = 0.499, P < 0.02). Treatment with 17β-estradiol showed reduction of CD4 T cell-induced apoptosis in PMW. Pure estrogen receptor antagonist ICI 172,780 abolished estrogen protection. Conclusions: Our results showed that the aging marker of DHEAS was lower in perimenopausal women, and that the low levels DHEAS, a endogenous major source of estrogen after menopause, induced CD4 T cell-induced endothelial apoptosis may be associated with ESR2. We concluded that low levels of DHEAS in perimenopausal women can be one factor that contributes to the acceleration of plaque erosion in atherosclerotic plaque and acute coronary syndromes.

Caffeine induces apoptosis of human umbilical vein endothelial cells through the caspase-9 pathway

Caffeine is known to modulate placental and fetal umbilical circulation. It is demonstrated that apoptosis of human umbilical vein endothelial cells (HUVECs) is associated with placental umbilical vascular diseases. The present study was conducted to investigate the effects of caffeine on apoptosis of HUVECs. Isolated HUVECs were cultured under serum-free conditions for 24 h, and then treated with graded concentrations of caffeine (30, 100 and 300 μM) for additional 24 h and 48 h. The number of viable HUVECs was determined by cell counting. Apoptotic HUVECs were assessed by Hoechst33342 dye staining. The expression of caspase-9, caspase-8, caspase-3 and poly(ADP-ribose) polymerase (PARP) was assessed by Western blot analysis. Caffeine induced a dose- and time-dependent decrease in the number of viable HUVECs. Caffeine at concentrations higher than 100 μM significantly increased the percentage of apoptotic HUVECs. Caffeine at concentrations higher than 100 μM significantly increased cleaved caspase-9, caspase-3 and PARP expression in HUVECs at 24-h treatment compared with untreated cultures, whereas 30 μM caffeine significantly increased only caspase-3 expression at 24 h. Caffeine did not affect cleaved caspase-8 expression at 48 h. These results suggest that high concentrations of caffeine inhibit cell growth of HUVECs and induce apoptosis through the caspase-9 pathway.

Tu-P7:177 Mechanism involved in the apoptosis of human umbilical vein endothelial cells induced by proteasome inhibitor MG132

Tu-P7:177 Mechanism involved in the apoptosis of human umbilical vein endothelial cells induced by proteasome inhibitor MG132

IFN-γ/JAK/STAT pathway-induced inhibition of DR4 and DR5 expression on endothelial cells is cancelled by cycloheximide-sensitive mechanism: Novel finding of cycloheximide-regulating death receptor expression

The pathway of interferon gamma (IFN-gamma-induced suppression in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated endothelial cell apoptosis was investigated. rTRAIL triggered apoptosis of human umbilical vein endothelial cells (HUVECs) in a type II cell death manner. IFN-gamma pretreatment significantly suppressed the expression of death receptor 4 (DR4) and DR5 on HUVECs, and inhibited apoptosis in response to TRAIL. IFN-gamma rapidly phosphorylated signal transducers and activators of transcription 1 (STAT1) and STAT6 but did not enhance phosphorylation of STAT3, Akt and extracellular signal-regulated kinase (ERK) and nuclear translocation of NF-kappaB p65. Janus kinase (JAK)-induced phosphorylation of STAT1/6 appeared to be crucial since chemical inhibition of JAK abolished phosphorylation of STAT1/6, down-regulation of DR4/DR5 expression and IFN-gamma-induced inhibition of TRAIL-mediated apoptosis. IFN-gamma/JAK/STAT-induced suppression was regulated by cycloheximide (CHX)-sensitive mechanism since the use of CHX mimicked the action of chemical inhibition of JAK in regard to DR4/DR5 expression as well as TRAIL-mediated endothelial cell apoptosis. We have not yet clarified precise mechanism, however, the present data provide a novel finding that IFN-gamma/JAK/STAT pathway elicits inhibition of TRAIL-mediated endothelial cell apoptosis through CHX-sensitive suppression of DR4/DR5.

The role of tyrosine phosphorylation in TNFα-induced apoptosis of Human Umbilical Vein Endothelial Cells (HUVECs)

The role of tyrosine phosphorylation in TNFα-induced apoptosis of Human Umbilical Vein Endothelial Cells (HUVECs)