Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pigment epithelium-derived factor (PEDF) has recently been shown to be involved in the pathogenesis of proliferative diabetic retinopathy. Atherosclerosis is an inflammatory-fibroproliferative disease as well. Oxidative stress plays a major role in retinopathy and atherosclerosis. Accordingly, we investigated effects of PEDF on reactive oxygen species (ROS) generation, NF-kappaB activation and interleukin (IL)-6 expression in TNF-alpha-exposed HUVEC. TNF-alpha significantly increased intracellular ROS generation, which was completely blocked by PEDF or diphenylene iodonium, an inhibitor of NADPH oxidase. Further, PEDF completely prevented the TNF-alpha-induced increase in NADPH oxidase activity. PEDF or an antioxidant, N-acetylcysteine, significantly inhibited the TNF-alpha-induced NF-kappaB activation. PEDF inhibited TNF-alpha-induced expression of IL-6 at both mRNA and protein levels. Moreover, TNF-alpha downregulated PEDF mRNA levels. Ligand blot analysis revealed that HUVEC possessed a membrane protein with binding affinity for PEDF. The results demonstrated that PEDF inhibited TNF-alpha-induced NF-kappaB activation and subsequent IL-6 overexpression in HUVEC by suppressing NADPH oxidase-mediated ROS generation. Our present study suggests that PEDF may play an important role in the development and progression of atherosclerosis.
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PMID:Pigment epithelium-derived factor inhibits TNF-alpha-induced interleukin-6 expression in endothelial cells by suppressing NADPH oxidase-mediated reactive oxygen species generation. 1527 19

The correct formation of new blood vessels from existing vasculature (angiogenesis) is essential for embryogenesis and the effective repair of damaged or wounded tissues. However, excessive and detrimental vascularization also occurs in neoplasia, promoting tumour growth and metastasis, as well as in proliferative diabetic retinopathy and atherosclerosis. Greater understanding of the mechanisms controlling the angiogenic process will allow optimization of wound healing, and provide mechanisms to inhibit vascularization in tumours and other diseases. Evidence supports a cascade of events in which the perturbation of one of the steps is sufficient to significantly inhibit neovascularization. The extracellular macromolecules, notably glycosaminoglycans (GAGs), are important mediators of angiogenesis. Hyaluronan (HA), a large, non-sulphated GAG, was first discovered in the vitreous of the eye [.], and is ubiquitously expressed in the extracellular matrix (ECM) of tissues. Native high molecular weight HA (n-HA) is anti-angiogenic, whereas HA degradation products (o-HA; 3-10 disaccharides) stimulate endothelial cell (EC) proliferation, migration and tube formation following activation of specific HA receptors in particular, CD44 and Receptor for HA-Mediated Motility (RHAMM, CD168). The involvement of HA in the regulation of angiogenesis makes it an attractive therapeutic target. We review the role of o-HA in modulation of angiogenesis during tissue injury, and vascular disease, focusing on receptor-mediated signal transduction pathways that have been evaluated.
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PMID:Hyaluronan-mediated angiogenesis in vascular disease: uncovering RHAMM and CD44 receptor signaling pathways. 1705 33

The investigation was undertaken to study the effect of the pentoxifylline retard dosage form Vasonit on ocular hemodynamics in patients with retinal vein occlusions and non-proliferative diabetic retinopathy (DR). Forty-two patients aged 45 to 75 years, including 20 patients (20 eyes) with retinal vein occlusion in the presence of hypertensive disease and atherosclerosis (Group 1) and 22 patients (44 years) with non-proliferative DR (Group 2), were examined. All the patients received the pentoxifylline retard dosage form Vasonit, 600 mg twice a day, for 2 months. After a course of pentoxifylline therapy, the patients were observed to have improved visual functions, positive clinical changes in the fundus of the eye as a reduction in the frequency and extent of retinal hemorrhages, in the degree of manifestations of macular edema, in the number of retinal microaneurysms and ischemic areas. The results of color Doppler mapping of ocular and orbital vessels are indicative of improved hemodynamics as an increase in the values of blood flow velocity and normalization of blood flow resistance and pulsation indices in the arteries supplying blood to the retina and optic nerve.
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PMID:[Role of pentoxifylline retard dosage forms in the correction of hemodynamic disorders in retinal venous occlusion and diabetic retinopathy]. 1780 53

Objective. To investigate the risk factors of DR in Chinese T2DM patients. Methods. 2009 patients with T2DM were included in this cross-sectional study. All patients underwent eye examination, and the DR stage was defined by an ophthalmologist. Correlation analysis was performed to evaluate the relation between DR and clinical variables. Logistic regression models were used to assess risk for those factors associated with DR. Results. A total of 597 T2DM patients (29.7%) had DR, of which 548 (27.3%) were nonproliferative diabetic retinopathy and 49 (2.4%) were proliferative diabetic retinopathy. Positive correlations were found between DR and duration of diabetes, systolic blood pressure (SBP), diastolic blood pressure, glycated hemoglobin, glycated albumin, 24 hurinary albumin excretion, peripheral atherosclerosis (PA), diabetes nephropathy (DN), diabetic peripheral neuropathy, and anemia. Negative correlations were found between DR and C-peptide and glomerular filtration rate. Logistic regression analysis revealed that duration of diabetes, SBP, DN, anemia, PA, and C-peptide were each independent risk factors of DR. Conclusion. The duration of diabetes, SBP, DN, anemia, and PA are positively associated with DR in Chinese T2DM patients, while C-peptide is negatively associated with DR. Monitoring and evaluation of these related factors will likely contribute to the prevention and treatment of DR.
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PMID:Factors associated with diabetic retinopathy in chinese patients with type 2 diabetes mellitus. 2284 79

Matrix metalloproteinases (MMPs) are large groups of zinc-dependent proteases that play an important role in many diseases and pathological processes such as cancer, angiogenesis, atherosclerosis, and vascular disease. Also, it was found that the expression of MMPs was high during the initial period of thrombosis in a rat model of traumatic deep vein thrombosis. Moreover, the presence of metalloproteinase activity and endogenous inhibitor activity in vitrectomy samples are associated with neovascularization of several retinal diseases such as exudative age related maculopathy, proliferative diabetic retinopathy, and central retinal vein occlusion. In this study, we aimed to investigate the possible association of the matrix metalloproteinase 2-1306C/T (rs 243865) and tissue inhibitors of matrix metalloproteinase 2 G-418C (rs 8179090) polymorphisms with the risk of retinal vein occlusion (RVO). Genomic DNA was extracted from peripheral leukocytes from ethylenediaminetetraacetic acid anticoagulated blood. Genotyping of the MMP2-1306C/T and TIMP2G-418C polymorphisms were performed using real-time polymerase chain reaction. The MMP2-1306 T allele carriers (CT + TT) had a significantly increased risk of RVO compared with the CC homozygotes (p < 0.001, odds ratio = 4.78; 95% CI = 2.85-8.09). After adjusting for hypertension, diabetes, hypertriglyceridemia, and hypercholesterolemia, MMP2-1306 T allele carriers (CT + TT) also had a significantly increased risk of RVO (B = 1.453; p < 0.001; odds ratio = 4.275; 95% CI:2.529-7.224). MMP2-1306C/T, but not TIMP2G-418C, gene variants are a risk factor for the development of retinal vein occlusion.
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PMID:Association of MMP2-1306C/T and TIMP2G-418C polymorphisms in retinal vein occlusion. 2379 66