Role In Endothelial Cell Damage Research Articles

The Role of Microvascular Obstruction and Intra-Myocardial Hemorrhage in Reperfusion Cardiac Injury. Analysis of Clinical Data.

Microvascular obstruction (MVO) of coronary arteries promotes an increase in mortality and major adverse cardiac events in patients with acute myocardial infarction (AMI) and percutaneous coronary intervention (PCI). Intramyocardial hemorrhage (IMH) is observed in 41-50% of patients with ST-segment elevation myocardial infarction and PCI. The occurrence of IMH is accompanied by inflammation. There is evidence that microthrombi are not involved in the development of MVO. The appearance of MVO is associated with infarct size, the duration of ischemia of the heart, and myocardial edema. However, there is no conclusive evidence that myocardial edema plays an important role in the development of MVO. There is evidence that platelets, inflammation, overload, neuropeptide Y, and endothelin-1 could be involved in the pathogenesis of MVO. The role of endothelial cell damage in MVO formation remains unclear in patients with AMI and PCI. It is unclear whether nitric oxide production is reduced in patients with MVO. Only indirect evidence on the involvement of inflammation in the development of MVO has been obtained. The role of reactive oxygen species (ROS) in the pathogenesis of MVO is not studied. The role of necroptosis and pyroptosis in the pathogenesis of MVO in patients with AMI and PCI is also not studied. The significance of the balance of thromboxane A2, vasopressin, angiotensin II, and prostacyclin in the formation of MVO is currently unknown. Conclusive evidence regarding the role of coronary artery spasm in the development of MVhasn't been established. Correlation analysis of the neuropeptide Y, endothelin-1 levels and the MVO size in patients with AMI and PCI has not previously been performed. It is unclear whether epinephrine aggravates reperfusion necrosis of cardiomyocytes. Dual antiplatelet therapy improves the efficacy of PCI in prevention of MVO. It is unknown whether epinephrine or L-type channel blockers result in the long-term improvement of coronary blood flow in patients with MVO.

Reperfusion cardiac injury. The role of microvascular obstruction

Microvascular obstruction (MVO) of coronary arteries increases the mortality rate and major adverse cardiac events in patients with acute myocardial infarction (AMI) and percutaneous coronary intervention (PCI). According to preliminary data platelets, inflammation, Ca2+ overload, neuropeptide Y, and endothelin-1 could be involved in the pathogenesis of MVO. Many questions related to the pathogenesis of MVO remain unanswered. The role of endothelial cell damage in the formation of MVO in patients with AMI and PCI is unknown. It is unclear whether nitric oxide (NO) production reduces or decreases sensitivity of smooth muscle cells of coronary arteries to NO in patients with MVO. It was obtained only indirect evidence on the involvement of inflammation in the development of MVO. The role of ROS in the pathogenesis of MVO is not studied. The role of necroptosis and pyroptosis in the pathogenesis of MVO in patients with AMI and PCI is also not studied.The significance of thromboxane A, vasopressin, angiotensin II, and prostacyclin in the formation of MVO is unknown before. It was not obtained conclusive evidence on the involvement of coronary artery spasm in the development of MVO. Correlation analysis of the neuropeptide Y, endothelin-1 levels and the MVO size in patients with AMI and PCI was not performed. It is not clear whether endogenous adrenaline exacerbates MVO or, conversely, prevents MVO.

Ferulic Acid Mitigates Radiation Injury in Human Umbilical Vein Endothelial Cells In Vitro via the Thrombomodulin Pathway.

Cell death and tissue injury occur as a result of radiation accidents and radiotherapy. The role of endothelial cell damage in mediating radiation-induced acute tissue injury has been extensively studied. We previously demonstrated that ferulic acid (FA) mitigates radiation-induced hematopoietic injury in mice and lessens radiation-induced oxidative damage in human umbilical vein endothelial cells (HUVECs). The purpose of the current study was to determine whether FA can protect HUVECs from radiation toxicity in a cell model via the thrombomodulin (Thbd) pathway, an anti-radiation pathway with anticoagulant, anti-inflammatory and antioxidant properties. HUVEC culture media was supplemented with FA 12 h before 4 Gy 60Co gamma irradiation. At 30 min postirradiation, the FA media was refreshed, then renewed once daily. HUVEC injury was assessed at day 5 postirradiation through cell proliferation analysis. Ferulic acid significantly ameliorated HUVEC radiation injury, as evidenced by increases in cell viability and angiogenesis and decreases in G2/M cell cycle arrest and levels of high mobility group box 1 protein (HMGB1), interleukin (IL)-6 and IL-8. These findings can be attributed to the effect of FA on the Thbd promoter, resulting in increased expression of Thbd and activated protein C with associated radioprotection. These observations indicate that FA intervention significantly ameliorates HUVEC radiation injury via the Thbd pathway. Therefore, FA could be further developed as a potential agent to mitigate radiation-induced damage.

Endothelial cell damage induces a blood–alveolus barrier breakdown in the development of radiation‐induced lung injury

To investigate the role of endothelial cell damage in radiation-induced lung injury. A total of 60 male Sprague-Dawley rats were irradiated to the right hemithorax with a single dose of 0, 7.0 or 14.4 Gy. Serial studies were performed before and at 1, 7, 30 and 90 days after radiation, respectively. Pathological studies were carried out to detect changes in the lung after irradiation. Western blot studies were conducted to detect the expression of CD34 and of CD105 and vascular endothelial growth factor (VEGF). Compared to controls, the irradiated rat lung showed a dose-dependent and time-dependent decrease in the expression of CD34. The level of CD105 was significantly reduced by irradiation except at 90 days after radiation. The expression of VEGF increased 1 day after radiation, and then decreased from day 30 onwards, to be lower than the control group at 90 days. Pulmonary fibrosis was observed at 90 days after 14.4 Gy exposure; however, most of these phenomena were not observed in the 7.0 Gy group. These results support the notion that endothelial cells play an important role in radiation-induced lung injury, and may be critical to breakdown of the blood-alveolus barrier and microcirculation dysfunction related to radiation-induced inflammation and fibrosis.

How does interferon‐α insult the vasculature? Let me count the ways

How does interferon‐α insult the vasculature? Let me count the ways

High Glucose and/or Free Fatty Acid Damage Vascular Endothelial Cells via Stimulating of NAD(P)H Oxidase-induced Superoxide Production from Neutrophils

Background: Oxidative stress and inflammation are important factors in the pathogenesis of diabetes and contribute to the development of diabetic complications. To understand the mechanisms that cause vascular complications in diabetes, we examined the effects of high glucose and/or free fatty ac ids on the production of superoxide from neutrophils and their role in endothelial cell damage. Methods: Human neutrophils were incubated in the media containing 5.5 m M D-glucose, 30 mM D-glucose, 3 nM oleic acid, or 30 μM oleic acid for 1 hour to evaluate superoxide production through NAD(P)H oxidase activation. Human aortic endothelial cells were co-cultured wit h neutrophils exposed to high glucose and oleic acid. We then measured neutrophil adhesion to endothelial cells, neutrophil activation and superoxide production, neutrophil-mediated endothelial cell cytotoxicity and subunits of neutrophil NAD(P)H oxidase. Results: After 1 hour of incubation with various concentrations of glucose and oleic acid, neutrophil adherence to high glucose and oleic acid-treated endothelial ce lls was significantly increased compared with adhesion to low glucose and oleic acid-treated endothelial cells. Incubation of neutrophils with glucose and free fatty acids increased superoxide production in a dose-dependent manner. High glucose and oleic acid treatment significantly increased expression of the membrane components of NAD(P)H oxidase of neutrophil (gp91 phox ). Endothelial cells co-cultured with neutrophils exposed to hi gh glucose and oleic acid showed increased cytolysis, which could be prevented by an antioxidant, N-acetylcysteine. Conclusion: These results suggest that high glucose and/orfree fatty acidsincrease injury of endothelial cells via stimulating NAD(P)H oxidase-induced superoxide production from neutrophils. (Korean Diabetes J 33:94-104, 2009)

Plasmodium falciparumMalaria: Reduction of Endothelial Cell Apoptosis In Vitro

Organ failure in Plasmodium falciparum malaria is associated with neutrophil activation and endothelial damage. This study investigates whether neutrophil-induced endothelial damage involves apoptosis and whether it can be prevented by neutralization of neutrophil secretory products. Endothelial cells from human umbilical veins were coincubated with neutrophils from healthy donors and with sera from eight patients with P. falciparum malaria, three patients with P. vivax malaria, and three healthy controls. Endothelial apoptosis was demonstrated by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) and annexin V staining. The rate of apoptosis of cells was markedly increased after incubation with patient serum compared to that with control serum. Apoptosis was most pronounced after incubation with sera from two patients with fatal cases of P. falciparum malaria, followed by sera of survivors with severe P. falciparum malaria and, finally, by sera of patients with mild P. falciparum and P. vivax malaria. Ascorbic acid, tocopherol, and ulinastatin reduced the apoptosis rate, but gabexate mesilate and pentoxifylline did not. Furthermore, in fatal P. falciparum malaria, apoptotic endothelial cells were identified in renal and pulmonary tissue by TUNEL staining. These findings show that apoptosis caused by neutrophil secretory products plays a major role in endothelial cell damage in malaria. The antioxidants ascorbic acid and tocopherol and the protease inhibitor ulinastatin can reduce malaria-associated endothelial apoptosis in vitro.

Geranylgeranylaceton prevents hydrogen peroxide induced retardation of angiogenesis

Background & Aim : Angiogenesis is one of the crucial events affecting ulcer healing. It has been reported that neutrophil-derived reactive oxygen species including hydrogen peroxide (HzOz) play an important role in endothelial cell damage leading to suppression of angiogenesis in the H.pylori-infected gastric mucosa. In this study, we aimed to investigate the protective effect of geranylgeranylaceton (GGA), a mucosal defensive agent, against endothelial cell injury caused by HzOz. Methods: HzOz (0.88mM) was added to human umbilical endothelial cells (HUVEC) cultured in DMEM F-12 / RPMIl640 medium containing 2 % FCS with or without 10M GGA that was added 12 h prior to the initiation of the experiments. Cell proliferation was assessed by BrdU staining and apoptotic cells were detected by the TUNEL method. The damage of actin was evaluated with rhodamine-phalloidin staining. To explore the mechanism(s) of the protective effect of GGA, production of prostaglandin E2 (PGE2) was measured by ELISA, expression of the transcription factor ETS-I was detected by RT-PCR, and the level of heat shock protein 70 (HSP70) was measured by Western blotting and immunohistochemistry. Results: Addition of HzOz reduced the growth of HUVEC by 87 %, from 42.5:t6.4 to 5.5:t 1.0 % BrdU staining index. Pre-treatment with GGA restored the cell growth by 60 % to 20.4:t2.3 %. Moreover, GGA prevented completely the HzOz-induced apoptosis (control 2.2+0.9, +HzOz 7.6:t1.7, GGA+HzOz 2.0:tl.l%). In the non-HzOz treated normal cells, polymerized actin was distributed abundantly beneath the plasma membrane and on the stressfibers. In marked contrast, HzOz-treatment reduced greatly polymerized actin. GGA diminished this HzOz-induced reduction of polymerized actin. Cytoplasmic HSP70 protein level was significantly higher in the GGA-treated group as compared to control whereas the production of PGE2 and expression of ETS-I were not altered by GGA pre-treatment. Conclusions: These results demonstrated that GGA prevents the HzOz-induced induction of apoptosis and retardation of proliferation in endothelial cells in vitro. It was postulated that this effect was due to upregulation of cellular HSP70. These results suggest that GGA might act as a muccosal protectant through preserving angiogenesis process during ulcer healing.

Pharmacological alteration of the lung vascular response to radiation

The role of endothelial cell damage in the development of radiation injury in the lung was investigated in rats. Vascular permeability-surface area product (PS) was measured as an indicator of the degree of endothelial cell damage in lungs of rats exposed to single dose hemithorax irradiation. Hemithorax irradiation was chosen to simulate clinical radiotherapy, in which only a portion of the lung is irradiated. In addition, it provided a control lung to compare to the irradiated lung. Radiation is postulated to lead to activation of several different biochemical pathways that result in lung injury and fibrosis. Many of these pathways can be specifically blocked with drugs. Thirteen different drugs were studied. Dexamethasone, indomethacin, cromolyn, cyproheptadine, Vitamin D 3, theophylline, and diethylcarbamazine were all effective at reducing lung PS on the irradiated side. Dexamethasone, Vitamin D 3, and iindomethacin also significantly reduced lung PS in the unirradiated lungs and in sham-irradiated rats. Captopril, cobra venom factor, penicillamine, trapidil, epsilon-amino caproic acid, and dapsone had no significant effect on lung PS after hemithorax irradiation. We conclude that the major pathways involved in early post-radiation lung injury involve; prostaglandin, leukotriene, and histamine release from macrophages and mast cells. Complement activation, proteolytic enzymes, and neutrophil migration do not seem to be important mediators of early postradiation lung injury.