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EC Proliferation (ec + proliferation)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Lipid-Like Nanoparticles for Small Interfering RNA Delivery to Endothelial Cells

ADVANCED FUNCTIONAL MATERIALS, Issue 19 2009
Seung-Woo Cho
Abstract Here, nanoparticles composed of lipid-like materials (lipidoids) to facilitate non-viral delivery of small interfering RNA (siRNA) to endothelial cells (ECs) are developed. Nanoparticles composed of siRNA and lipidoids with small size (,200,nm) and positive charge (,34,mV) are formed by self-assembly of lipidoids and siRNA. Ten lipidoids are synthesized and screened for their ability to facilitate the delivery of siRNA into ECs. Particles composed of leading lipidoids show significantly better delivery to ECs than a leading commercially available transfection reagent, Lipofectamine 2000. As a model of potential therapeutic application, nanoparticles composed of the top performing lipidoid, NA114, are studied for their ability to deliver siRNA targeting anti-angiogenic factor (SHP-1) to human ECs. Silencing of SHP-1 expression significantly enhances EC proliferation and decreases EC apoptosis under a simulated ischemic condition. [source]

Ethanol Modulation of TNF-alpha Biosynthesis and Signaling in Endothelial Cells: Synergistic Augmentation of TNF-alpha Mediated Endothelial Cell Dysfunctions by Chronic Ethanol

ALCOHOLISM, Issue 6 2005
Corinne Luedemann
Despite reported cardio-protective effects of low alcohol intake, chronic alcoholism remains a risk factor in the pathogenesis of coronary artery disease. Dose related bimodal effects of alcohol on cardiovascular system might reflect contrasting influences of light versus heavy alcohol consumption on the vascular endothelium. Chronic ethanol induced damage to various organs has been linked to the increased release of TNF-alpha (TNF). We have previously shown that TNF, expressed at the sites of arterial injury, suppresses re-endothelialization of denuded arteries and inhibits endothelial cell (EC) proliferation in vitro. Here we report that in vitro chronic ethanol exposure enhances agonist-induced TNF mRNA and protein expression in EC. Ethanol-mediated increment in TNF expression involves increased de novo transcription without affecting mRNA stability. DNA binding assays revealed that ethanol-induced TNF up regulation was AP1 dependent. Functionally, TNF induced EC dysfunction, including reduced proliferation, migration and cyclin A expression, were all markedly enhanced in the presence of ethanol. Additionally, expression of cyclin D1 was significantly attenuated in cells co-treated with TNF and ethanol while each treatment alone had little effect on cyclin D1 expression. Furthermore, exposure to ethanol potentiated and prolonged agonist-induced activation of JNK. Inhibition of JNK by over-expression of dominant negative JNK1 substantially reversed ethanol/TNF-mediated inhibition of cyclin A expression and EC proliferation, suggesting modulation of JNK1 signaling as the mechanism for ethanol/TNF-induced EC dysfunctions. Taken together, these data indicate that chronic ethanol consumption may negatively influence post angioplasty re-endothelialization thereby contributing to the development of restenosis. [source]

Inflammation and angiogenesis in osteoarthritis

ARTHRITIS & RHEUMATISM, Issue 8 2003
L. Haywood
Objective To quantify the relationship between inflammation and angiogenesis in synovial tissue from patients with osteoarthritis (OA). Methods Hematoxylin and eosin staining and histologic grading for inflammation were performed for 104 patients who met the American College of Rheumatology criteria for OA and had undergone total joint replacement or arthroscopy. A purposive sample of synovial specimens obtained from 70 patients was used for further analysis. Vascular endothelium, endothelial cell (EC) proliferating nuclei, macrophages, and vascular endothelial growth factor (VEGF) were detected by immunohistochemical analysis. Angiogenesis (EC proliferation, EC fractional area), macrophage fractional area, and VEGF immunoreactivity were measured using computer-assisted image analysis. Double immunofluorescence histochemical analysis was used to determine the cellular localization of VEGF. Radiographic scores for joint space narrowing and osteophyte formation in the knee were also assessed. Results Synovial tissue samples from 32 (31%) of 104 patients with OA showed severe inflammation; thickened intimal lining and associated lymphoid aggregates were often observed. The EC fractional area, EC proliferation, and VEGF immunoreactivity all increased with increasing histologic inflammation grade and increasing macrophage fractional area. In the synovial intimal lining, VEGF immunoreactivity was localized to macrophages and increased with increasing EC fractional area and angiogenesis. No inflammation or angiogenic indices were significantly correlated with radiographic scores. Conclusion Inflammation and angiogenesis in the synovium are associated with OA. The angiogenic growth factor VEGF generated by the inflamed synovium may promote angiogenesis, thereby contributing to inflammation in OA. [source]

The role of HIF-1 alfa in apoptosis and proliferative retinopathy

ACTA OPHTHALMOLOGICA, Issue 2009
R FERNANDES
Purpose In diabetic retinal capillaries, the earlier morphological changes include pericyte loss and acellular capillary formation. These processes are regulated by interactions among a number of pro- and antiangiogenic factors, including vascular endothelial growth factor (VEGF) and Angiopoietin-2 (Ang-2). We hypothesize that increased levels of methylglyoxal (MGO) in RPE cells disrupts the balance of VEGF/Ang-2 promoting endothelial cell death and vessel regression. Methods Rats with moderate T2D, and retinal cell lines of epithelium (RPE) and endothelium (EC) were used. MGO levels were determined by HPLC. Immunohistochemical analysis was performed in retinas stained for VEGF and Ang-2. RPE cells were incubated with MGO in hypoxic conditions and the level of VEGF and Ang-2 was assessed by ELISA. EC were subsequently treated with the pre-conditioned media of the RPE cells. Cell death was determined by WB against Bax and Bcl-2, while EC proliferation was assessed by BrdU-incorporation and fibrin gel angiogenic assays. Results Hyperglycemia increases the levels of MGO in retinas and RPE cells. MGO increases the levels of Ang-2 and strongly decreases the levels of VEGF in response to hypoxia. VEGF downregulation appears to result both from increased HIF-1, degradation and low HIF-1 transcriptional activity. The MGO-induced imbalance in the VEGF/Ang-2 significantly increases the expression of Bax and decreases the levels of Bcl-2. Consistently, this imbalance leads to decreased proliferation of the EC. Conclusion In diabetic retinopathy, accumulation of MGO may play a role in VEGF/Ang-2 imbalance, triggering the activation of the apoptotic cascade which induces decreased proliferation of retinal endothelial cells and as a consequence vessels regression [source]