Endothelial injury in the initiation and progression of vascular disorders

Tesfamariam, Belay; DeFelice, Albert

doi:10.1016/j.vph.2006.11.005

Cited by 134 publications

(117 citation statements)

References 43 publications

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“…Although our study does not fully clarify the plausible mechanism of association of CRP with stent thrombosis, the possible explanations include the association of CRP with platelet and clotting system activation, 23 local inflammation in the vessel wall, 24 endothelial dysfunction, 25 hypersensitivity reactions, 26 and new plaque rupture either adjacent to or within the stented site, 27 all of which have also been suggested as potential causes of DES-related thrombosis. Biologically, CRP mediates enhanced expression of adhesion molecules, a potent chemoattractant, and plasminogen activator inhibitor-1 and a reduction in nitric oxide production, thereby altering the vascular equilibrium toward a proinflammatory, prothrombotic, and vasoconstrictive state.…”

Section: Discussionmentioning

confidence: 66%

C-Reactive Protein and the Risk of Stent Thrombosis and Cardiovascular Events After Drug-Eluting Stent Implantation

Park

Yun²,

Lee³

et al. 2009

Circulation

104

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Background-Although C-reactive protein (CRP) has been proposed as a useful biomarker for predicting atherothrombosis, the association between CRP and stent thrombosis after drug-eluting stent implantation has not been defined. Methods and Results-We prospectively evaluated 2691 patients treated with drug-eluting stents who had a baseline CRP measurement. The primary outcome was stent thrombosis; secondary outcomes were death, myocardial infarction (MI), death or MI, and target vessel revascularization. During follow-up (median, 3.9 years), 32 patients had definite or probable stent thrombosis, 137 patients died, 227 had an MI, and 195 underwent target vessel revascularization. In multivariable Cox proportional-hazards models, elevated levels of CRP were significantly associated with increased risk of stent thrombosis (hazard ratio, 3.86; 95% confidence interval, 1.82 to 8.18; PϽ0.001). Elevated CRP levels also significantly predicted the risks of death (hazard ratio, 1.61; 95% confidence interval, 1.13 to 2.28; Pϭ0.008), MI (hazard ratio, 1.63; 95% confidence interval, 1.25 to 2.12; Pϭ0.001), and death or MI (hazard ratio, 1.61; 95% confidence interval, 1.29 to 2.00; PϽ0.001) but not target vessel revascularization (hazard ratio, 1.20; 95% confidence interval, 0.90 to 1.61; Pϭ0.21). The incorporation of CRP into a model with patient, lesion, and procedural factors resulted in a significant increase in the C statistic for the prediction of stent thrombosis, MI, and the composite of death or MI. Conclusions-Elevated CRP levels were significantly associated with increased risks of stent thrombosis, death, and MI in patients receiving drug-eluting stents, suggesting the usefulness of inflammatory risk assessment with CRP. Given the relatively infrequent occurrence of stent thrombosis, death, and MI, larger studies with longer-term follow-up are required to confirm the novel relationship.

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Section: Discussionmentioning

confidence: 66%

C-Reactive Protein and the Risk of Stent Thrombosis and Cardiovascular Events After Drug-Eluting Stent Implantation

Park

Yun²,

Lee³

et al. 2009

Circulation

104

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“…23 The endothelium, located at the interface between the vessel wall and blood circulation, acts as a barrier between vascular tissue and blood components and modulates traffic of cells and related compounds between them. 24 24 -26 These locally expressed adhesion molecules and cytokines/chemokines activate neutrophils and generate reactive oxygen species (ROS), promoting endothelial inflammation. In this way, endothelial dysfunction integrally associates with the inflammatory process to culminate vascular injury and pose threats to normal vascular function.…”

Section: Ppar-␥ Activation/inactivation In Vascular Ecsmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor-γ–Mediated Effects in the Vasculature

Duan

Usher

Mortensen

2008

Circulation Research

254

205

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Abstract-Peroxisome proliferator-activated receptor (PPAR)-␥ is a nuclear receptor and transcription factor in the steroidsuperfamily. PPAR-␥ agonists, the thiazolidinediones, are clinically used to treat type 2 diabetes. In addition to its function in adipogenesis and increasing insulin sensitivity, PPAR-␥ also plays critical roles in the vasculature. In vascular endothelial cells, PPAR-␥ activation inhibits endothelial inflammation by suppressing inflammatory gene expression and therefore improves endothelial dysfunction. In vascular smooth muscle cells, PPAR-␥ activation inhibits proliferation and migration and promotes apoptosis. In macrophages, PPAR-␥ activation suppresses inflammation by regulating gene expression and increases cholesterol uptake and efflux. A recurring theme in many cell types is the modulation of the innate immunity system particularly through altering the activity of the nuclear factor B. This system is likely to be even more prominent in modulating disease in vascular cells V ascular complications such as atherosclerosis and hypertension are primary causes to mortality associated with diabetes and obesity. With the increasing prevalence of diabetes and obesity, 1,2 vascular protection is critical to decreasing this mortality and improving public health as a whole. To accomplish this protection, one member in the nuclear receptor superfamily, peroxisome proliferator-activated receptor (PPAR)-␥, has emerged as an important player. PPAR-␥ ligands, thiazolidinediones (TZDs), are clinically used for type 2 diabetes. It is clear that improving glucose and lipid homeostasis by treating diabetes or insulin resistance has beneficial effects on cardiovascular diseases.

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“…Since vascular endothelial cells are first exposed to drugs administered intravascularly, the endothelial cell dysfunction may contribute to vascular disorders (8). However, the effect of GM on endothelial cells has not been studied.…”

Section: Introductionmentioning

confidence: 99%

Characteristics of Gabexate Mesilate–Induced Cell Injury in Porcine Aorta Endothelial Cells

et al. 2008

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Abstract. Gabexate mesilate (GM), a serine protease inhibitor, often causes severe vascular injury, when injected in high concentration. In the present study, we investigated the mechanisms for the cytotoxicity of GM on porcine aorta endothelial cells (PAECs). GM (0.5 -5.0 mM) decreased cell viability in a dose-dependent manner and caused cell injury, whilst nafamostat mesilate (NM), another serine protease inhibitor, or mesilate itself had no effect on cell viability. zVAD-fmk, a pancaspase inhibitor, or zDEVD-fmk, a caspase-3 inhibitor, did not affect the GM (1.5 mM)-induced decrease of cell viability. Apoptotic cells or DNA fragmentation were also not observed after GM treatment. Moreover, Ca 2+ chelators, a nitric oxide (NO) synthase inhibitor, antioxidants, and radical scavengers had no effect on the GM-induced cell injury. On the other hand, cellular ATP content was decreased in the GM (2.0 mM)-treated cells. Surprisingly, GM (2.0 mM) immediately increased cellular uptake of propidium iodine. These findings suggest that GM induces necrotic cell death via injury of the cell membrane.

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Endothelial injury in the initiation and progression of vascular disorders

Cited by 134 publications

References 43 publications

C-Reactive Protein and the Risk of Stent Thrombosis and Cardiovascular Events After Drug-Eluting Stent Implantation

C-Reactive Protein and the Risk of Stent Thrombosis and Cardiovascular Events After Drug-Eluting Stent Implantation

Peroxisome Proliferator-Activated Receptor-γ–Mediated Effects in the Vasculature

Characteristics of Gabexate Mesilate–Induced Cell Injury in Porcine Aorta Endothelial Cells

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