The interferon-inducible gene IFI16, a member of the HIN200 family, triggers primary endothelial cell apoptosis through caspase 2 and caspase 3 pathway

Cytokine ◽  
2009 ◽  
Vol 48 (1-2) ◽  
pp. 85
Author(s):  
Francesca Gugliesi ◽  
Marco De Andrea ◽  
Michele Mondini ◽  
Paola Cappello ◽  
Mirella Giovarelli ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Endothelial Cell Apoptosis ◽  
Caspase 2 ◽  
Inducible Gene

25-Hydroxycholesterol impairs endothelial function and vasodilation by uncoupling and inhibiting endothelial nitric oxide synthase

2016 ◽  
Vol 311 (4) ◽  
pp. E781-E790 ◽  
Author(s):  
Zhi-Jun Ou ◽  
Jing Chen ◽  
Wei-Ping Dai ◽  
Xiang Liu ◽  
Yin-Ke Yang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Endothelial Function ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Immunoblot Analysis ◽  
Tube Formation ◽  
Endothelial Cell Proliferation ◽  
No Production ◽  
Endothelial Cell Apoptosis ◽  
Caspase 9

Endothelial dysfunction is a key early step in atherosclerosis. 25-Hydroxycholesterol (25-OHC) is found in atherosclerotic lesions. However, whether 25-OHC promotes atherosclerosis is unclear. Here, we hypothesized that 25-OHC, a proinflammatory lipid, can impair endothelial function, which may play an important role in atherosclerosis. Bovine aortic endothelial cells were incubated with 25-OHC. Endothelial cell proliferation, migration, and tube formation were measured. Nitric oxide (NO) production and superoxide anion generation were determined. The expression and phosphorylation of endothelial NO synthase (eNOS) and Akt as well as the association of eNOS and heat shock protein (HSP)90 were detected by immunoblot analysis and immunoprecipitation. Endothelial cell apoptosis was monitored by TUNEL staining and caspase-3 activity, and expression of Bcl-2, Bax, cleaved caspase-9, and cleaved caspase-3 were detected by immunoblot analysis. Finally, aortic rings from Sprague-Dawley rats were isolated and treated with 25-OHC, and endothelium-dependent vasodilation was evaluated. 25-OHC significantly inhibited endothelial cell proliferation, migration, and tube formation. 25-OHC markedly decreased NO production and increased superoxide anion generation. 25-OHC reduced the phosphorylation of Akt and eNOS and the association of eNOS and HSP90. 25-OHC also enhanced endothelial cell apoptosis by decreasing Bcl-2 expression and increasing cleaved caspase-9 and cleaved caspase-3 expressions as well as caspase-3 activity. 25-OHC impaired endothelium-dependent vasodilation. These data demonstrated that 25-OHC could impair endothelial function by uncoupling and inhibiting eNOS activity as well as by inducing endothelial cell apoptosis. Our findings indicate that 25-OHC may play an important role in regulating atherosclerosis.

Simvastatin causes endothelial cell apoptosis and attenuates severe pulmonary hypertension

2006 ◽  
Vol 291 (4) ◽  
pp. L668-L676 ◽  
Author(s):  
Laimute Taraseviciene-Stewart ◽  
Robertas Scerbavicius ◽  
Kang-Hyeon Choe ◽  
Carlyne Cool ◽  
Kathy Wood ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Endothelial Cell ◽  
Right Ventricular ◽  
Cell Apoptosis ◽  
Ventricular Hypertrophy ◽  
Caspase 3 ◽  
Right Ventricular Hypertrophy ◽  
Severe Pulmonary Hypertension ◽  
Endothelial Cell Apoptosis ◽  
Microvascular Endothelial

Severe pulmonary hypertension (SPH) is characterized by precapillary arteriolar lumen obliteration, dramatic right ventricular hypertrophy, and pericardial effusion. Our recently published rat model of SPH recapitulates major components of the human disease. We used this model to develop new treatment strategies for SPH. SPH in rats was induced using VEGF receptor blockade in combination with chronic hypoxia. A large variety of drugs used in this study, including anticancer drugs (cyclophosphamide and paclitaxel), the angiotensin-converting enzyme inhibitor lisinopril, the antiangiogenic agent thalidomide, and the peroxisome proliferator-actived receptor-γ agonist PGJ2, failed to decrease mean pulmonary artery pressure (PAP) or right ventricular hypertrophy. In contrast, treatment of rats with established SPH with simvastatin markedly reduced mean PAP and right ventricular hypertrophy, and this reduction was associated with caspase-3 activation and pulmonary microvascular endothelial cell apoptosis. Simvastatin partially restored caveolin-1, caveolin-2, and phospho-caveolin expression in vessel walls. In rat primary pulmonary microvascular endothelial cells, simvastatin induced caspase 3 activation and Rac 1 expression while suppressing Rho A and attenuated levels of Akt and ERK phosphorylation. We conclude that simvastatin is effective in inducing apoptosis in hyperproliferative pulmonary vascular lesions and could be considered as a potential drug for treatment of human SPH.

scholarly journals The Src family tyrosine kinases src and yes have differential effects on inflammation-induced apoptosis in human pulmonary microvascular endothelial cells

2016 ◽  
Vol 310 (9) ◽  
pp. L880-L888 ◽  
Author(s):  
Leif D. Nelin ◽  
Hilary A. White ◽  
Yi Jin ◽  
Jennifer K. Trittmann ◽  
Bernadette Chen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Microvascular Endothelial Cells ◽  
Erk Pathway ◽  
Endothelial Cell Apoptosis ◽  
Phosphatidylinositol 3 Kinase ◽  
Erk Activation ◽  
Differential Effects

Endothelial cells are essential for normal lung function: they sense and respond to circulating factors and hemodynamic alterations. In inflammatory lung diseases such as acute respiratory distress syndrome, endothelial cell apoptosis is an inciting event in pathogenesis and a prominent pathological feature. Endothelial cell apoptosis is mediated by circulating inflammatory factors, which bind to receptors on the cell surface, activating signal transduction pathways, leading to caspase-3-mediated apoptosis. We hypothesized that yes and src have differential effects on caspase-3 activation in human pulmonary microvascular endothelial cells (hPMVEC) due to differential downstream signaling effects. To test this hypothesis, hPMVEC were treated with siRNA against src (siRNAsrc), siRNA against yes (siRNAyes), or their respective scramble controls. After recovery, the hPMVEC were treated with cytomix (LPS, IL-1β, TNF-α, and IFN-γ). Treatment with cytomix induced activation of the extracellular signal-regulated kinase (ERK) pathway and caspase-3-mediated apoptosis. Treatment with siRNAsrc blunted cytomix-induced ERK activation and enhanced cleaved caspase-3 levels, while treatment with siRNAyes enhanced cytomix-induced ERK activation and attenuated levels of cleaved caspase-3. Inhibition of the ERK pathway using U0126 enhanced cytomix-induced caspase-3 activity. Treatment of hPMVEC with cytomix induced Akt activation, which was inhibited by siRNAsrc. Inhibition of the phosphatidylinositol 3-kinase/Akt pathway using LY294002 prevented cytomix-induced ERK activation and augmented cytomix-induced caspase-3 cleavage. Together, our data demonstrate that, in hPMVEC, yes activation blunts the ERK cascade in response to cytomix, resulting in greater apoptosis, while cytomix-induced src activation induces the phosphatidylinositol 3-kinase pathway, which leads to activation of Akt and ERK and attenuation of apoptosis.

scholarly journals α-1 Antitrypsin Inhibits Caspase-3 Activity, Preventing Lung Endothelial Cell Apoptosis

2006 ◽  
Vol 169 (4) ◽  
pp. 1155-1166 ◽  
Author(s):  
Irina Petrache ◽  
Iwona Fijalkowska ◽  
Terry R. Medler ◽  
Jarrett Skirball ◽  
Pedro Cruz ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Endothelial Cell Apoptosis

scholarly journals Uric acid promotes oxidative stress and enhances vascular endothelial cell apoptosis in rats with middle cerebral artery occlusion

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Chengfu Song ◽  
Xiangdong Zhao
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Vascular Endothelial Cell ◽  
Artery Occlusion ◽  
Vascular Endothelial ◽  
Endothelial Cell Apoptosis ◽  
Related Factors ◽  
Cerebral Artery Occlusion

In patients with cerebral infarction (CI), elevated serum uric acid (UA) level may exacerbate the occurrence and development of carotid atherosclerosis (AS). Our study intended to explore the underlying mechanism. We enrolled 86 patients with CI, and divided them into four groups: Non-AS, AS-mild, AS-moderate, and AS-severe groups; the levels of UA and oxidative stress-related factors in serum were detected. The middle cerebral artery occlusion (MCAO) model was used to stimulate CI in rats, and different doses of UA were administrated. The levels of oxidative stress-related factors in serum were detected. Hematoxylin & eosin (H&E) staining was used to observe the morphological alterations, and the apoptotic cell death detection kit was used to detect apoptotic cells. Increased UA concentration and enhanced oxidative stress were found in AS patients. H&E staining results showed that UA treatment exacerbated morphological damage in rats with MCAO, promoted oxidative stress, and enhanced vascular endothelial cell apoptosis in rats with MCAO.

Maternal Anti-HPA-1a Antibodies Increase Endothelial Cell Apoptosis and Permeability

2021 ◽  
pp. 1-9
Author(s):  
Rima Dardik ◽  
Ophira Salomon
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Intracranial Hemorrhage ◽  
Cell Apoptosis ◽  
Endothelial Damage ◽  
Αvβ3 Integrin ◽  
Endothelial Cell Apoptosis ◽  
Vascular Beds ◽  
Alloimmune Thrombocytopenia

Intracranial hemorrhage (ICH) associated with fetal/neonatal alloimmune thrombocytopenia (FNAIT) is attributed mainly to endothelial damage caused by binding of maternal anti-HPA-1a antibodies to the αvβ3 integrin on endothelial cells (ECs). We examined the effect of anti-HPA-1a antibodies on EC function using 2 EC lines from different vascular beds, HMVEC of dermal origin and hCMEC/D3 of cerebral origin. Anti-HPA-1a sera significantly increased apoptosis in both HMVEC and hCMEC/D3 cells and permeability in hCMEC/D3 cells only. This increase in both apoptosis and permeability was significantly inhibited by a monoclonal anti-β3 antibody (SZ21) binding to the HPA-1a epitope. Our results indicate that (1) maternal anti-HPA-1a antibodies impair EC function by increasing apoptosis and permeability and (2) ECs from different vascular beds vary in their susceptibility to pathological effects elicited by maternal anti-HPA-1a antibodies on EC permeability. Examination of maternal anti-HPA-1a antibodies for their effect on EC permeability may predict potential ICH associated with FNAIT.

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