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Angiogenesis and hypertensive retinopathy

Angiogenesis and hypertensive retinopathy

ab OCT at presentation Angiogenesis and hypertensive retinopathy Angiogeenesis clinic showing reduction of central retinal thickness in the RE and retinal thickness reduction temporally to the fovea in the LE. Ann N Y Acad Sci. Clin Immunol. Angiogenesis and hypertensive retinopathy

Angiogenesis and hypertensive retinopathy -

Recent studies also suggest that the negative effects of VEGF are amplified in the settings of endothelial dysfunction and low nitric oxide NO levels, which are a common feature of hypertension. In our study statin treated individuals had higher serum levels of VEGF, suggesting that statins stimulate VEGF production.

Nevertheless, despite the percentage of statin treated individuals was higher in the control group, healthy individuals had lower serum concentration of VEGF than hypertensive patients.

This indicates that statin treatment did not obscure the results and suggests that if all studied subjects were not on statin therapy, the differences in VEGF levels between healthy and hypertensive subjects would be even more pronounced.

These observations underline the significance and utility of VEGF as a marker of hypertension and potential predictor of its complications. In addition, these data shed new light on consequences of statin therapy. For several years this group of drugs was considered to have beneficial anti-inflammatory impact [ 42 , 61 — 62 ].

Our data are in accordance with these recent reports and seems to partially explain why statins may be involved in carcinogenesis. In our study individuals treated with statins had increased serum levels of VEGF that is a known mediator of tumor growth and metastases, while anti-VEGF drugs have been used for years as effective therapy of several cancers [ 67 — 70 ].

According to our knowledge our study is the first suggesting that statins may increase production of VEGF, but can be supported by observations of Llevadot and Asahara who found that statins promote angiogenesis and vasculogenesis in a way similar to VEGF [ 71 ].

In summary, in the present study we found that hypertensive patients had higher serum levels of endostatin that is a potent angiogensis inhibitor and lower serum concentration of pro-angiogenic bFGF and angiogenin than healthy individuals.

As angiogenin protects blood vessels from negative effects of inflammation, has cytoprotective potential, is an important inducer of new blood vessel formation and is required for pro-angiogenic activity of other angiogenesis stimulators, its decreased production in hypertensive patients may play an important role in pathogenesis of hypertension and its complications.

Concomitantly, hypertension was accompanied by increased serum concentration of IL-8 and VEGF that reflects inflammatory response and abnormal angiogenesis. The phenomenon was the most pronounced in uncontrolled hypertension.

These data all together show that qualitative and quantitative changes in pro-angiogenic and anti-angiogenic factors in the background of inflammation are the hallmarks of arterial hypertension. The file describes the Cytometric Bead Array CBA technique used for measurement of serum VEGF, IL-8, and bFGF levels.

Figure briefly describes the method of cytometric measurement of serum concentration of VEGF, IL-8 and bFGF with Cytometric Bead Array CBA.

A FSC-A vs SSC-A dot plot shows a mix of three types of beads used for the measurement of VEGF, IL-8 and bFGF. Cell conglomerates visible as black dots are excluded from the analysis gate.

B Dot plot visualizes position of each group of beads on APC-A and APC-Cy7-A axes. Each bead set has different alphanumeric position on the dot-plot. C-D APC-A vs PE-A dot plots show exemplary results obtained for 2 different samples. Various concentrations of VEGF, IL-8, and bFGF are visualized on PE-A axis.

The higher fluorescence intensity of PE detection reagent, the higher concentration of the analyte. Serum concentrations of endostatin, VEGF, IL-8, angiogenin and bFGF were re-analyzed in order to express the amount of each cytokine in relation to the total serum protein level.

Multiple regression analysis was used to assess the influence of independent predictors such as: age, BMI, triglycerides and LDL on serum levels of VEGF.

Multiple regression analysis was used to assess the influence of independent predictors such as: age, BMI, triglycerides and LDL on serum levels of IL Multiple regression analysis was used to assess the influence of independent predictors such as: age, BMI, triglycerides and LDL on serum levels of angiogenin.

Multiple regression analysis was used to assess the influence of independent predictors such as: age, BMI, triglycerides and LDL on serum levels of bFGF. Multiple regression analysis was used to assess the influence of independent predictors such as: age, BMI, triglycerides and LDL on serum levels of endostatin.

Conceived and designed the experiments: NMT JS. Performed the experiments: NMT AK TK. Analyzed the data: NMT AK AM. Wrote the paper: NMT.

Clinical assessment of the patients and clinical data acquisition: MRG. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Article Authors Metrics Comments Media Coverage Reader Comments Figures. Abstract Objective Hypertension is the most common cardiovascular disease and the main risk factor for stroke, peripheral arterial disease, arterial aneurysms and kidney disease.

Materials and Methods 82 patients diagnosed with hypertension and 34 healthy volunteers were recruited to the study. Results Hypertensive patients were characterized by increased serum concentration of endostatin which is an anti-angiogenic factor. Conclusions Presented results show that hypertension is characterized by imbalance of pro-angiogenic and anti-angiogenic factors in the background of inflammation.

This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Data Availability: All relevant data are within the paper.

Introduction Arterial hypertension is the most common cardiovascular disease. Methods Patients A total of 82 consecutive patients with arterial hypertension treated at the Department of Family Medicine of Medical University in Gdansk in Poland were recruited.

Download: PPT. Table 1. Clinical and laboratory characteristics of the investigated groups. Sample preparation Serum was obtained from blood samples after centrifugation at xg for 15 minutes. Statistical analysis The results were calculated with Statistica Fig 4. Control of hypertension and serum concentration of cytokines.

Obesity does not affect endostatin, VEGF, IL-8, angiogenin and bFGF levels in serum of hypertensive and healthy individuals As previous studies suggested that production of certain cytokines can be affected by age, obesity and serum lipids [ 37 — 41 ] we aimed to verify if these factors affect also endostatin, VEGF, IL-8, angiogenin and bFGF measured in our study.

Statin treatment is associated with higher serum levels of VEGF In hypertensive and control group Discussion The current study shows that arterial hypertension is characterized by imbalance of pro-angiogenic versus anti-angiogenic factors. Supporting Information. S1 Appendix. Detailed description of measurement of VEGF, IL-8 and bFGF levels with flow cytometry.

s DOC. S1 Fig. Cytometric measurement of VEGF, IL-8 and bFGF. s TIF. S2 Fig. Serum concentration of endostatin, VEGF, IL-8, angiogenin and bFGF in relation to the amount of total serum protein. S1 Table. Assessment of the impact of age, BMI and serum lipid levels on serum VEGF concentration.

S2 Table. Assessment of the impact of age, BMI and serum lipid levels on serum IL-8 concentration. S3 Table. Assessment of the impact of age, BMI and serum lipid levels on serum angiogenin concentration. S4 Table. Assessment of the impact of age, BMI and serum lipid levels on serum bFGF concentration.

S5 Table. Assessment of the impact of age, BMI and serum lipid levels on serum endostatin concentration. Author Contributions Conceived and designed the experiments: NMT JS.

References 1. Félétou M, Vanhoutte PM. Endothelial dysfunction: a multifaceted disorder The Wiggers Award Lecture. Am J Physiol Heart Circ Physiol. Bobik A. J Hypertens. Touyz RM. Intracellular mechanisms involved in vascular remodelling of resistance arteries in hypertension: role of angiotensin II.

Exp Physiol. Humar R, Zimmerli L, Battegay E. Angiogenesis and hypertension: an update. J Hum Hypertens. Maitland ML, Bakris GL, Black HR, Chen HX, Durand JB, Elliott WJ, et al.

Initial assessment, surveillance and management of blood pressure patients receiving vascular endothelial growth factor signalling pathway inhibitors. J Natl Cancer Inst. Emanueli C, Salis MB, Stacca T, Gaspa L, Chao J, Chao L, et al. Rescue of impaired angiogenesis in spontaneously hypertensive rats by intramuscular human tissue kallikrein gene transfer.

Belgore FM, Lip GY, Bareford D, Wadley M, Stonelake P, Blann AD. Plasma levels of vascular endothelial growth factor VEGF and its receptor, Flt-1, in haematological cancers: a comparison with breast cancer. Am J Hematol. Rusiecka E, Drożdż J. Terapia naczyniowa. Pol Przeg Kardiol. View Article Google Scholar 9.

Engstrom G, Lind P, Hedblad B, Stavenow L, Janzon L, Lindgärde F. Long-term effects of inflammation-sensitive plasma proteins and systolic blood pressure on incidence of stroke. Pauletto P, Rattazzi M. Inflammation and hypertension: the search for a link. Nephrol Dial Transplant. Leong XF, Ng CY, Badiah B, Das S.

Association between hypertension and periodontitis: possible mechanisms. Sci World J. Srivastava S, Terjung RL, Yang HT. Basic fibroblast growth factor increases collateral blood flow in spontaneously hypertensive rats.

Marek N, Raczyńska K, Siebert J, Myśliwiec M, Zorena K, Myśliwska J, et al. Decreased angiogenin concentration in vitreous and serum in proliferative diabetic retinopathy. Microvasc Res. Siebert J, Reiwer-Gostomska M, Mysliwska J, Marek N, Raczynska K, Glasner R.

Glycemic control influences serum angiogenin concentrations in patients with type 2 diabetes. Diabetes Care. Debnath J, Dasgupta S, Pathak T.

Amino and carboxy functionalized modified nucleosides: a potential class of inhibitors for angiogenin. Bioorg Chem. Tello-Montoliu A, Patel JV, Lip GY. Angiogenin: a review of the pathophysiology and potential clinical applications.

J Thromb Haemost. A, The concentration of VEGF in aqueous humor geometric mean, ETDRS indicates Early Treatment Diabetic Retinopathy Study. Concentration of endostatin and severity of diabetic retinopathy DR. A, The concentration of endostatin in aqueous humor mean, 2. B, The concentration of endostatin in the vitreous fluid mean, 4.

The relationship between the vitreous concentrations of vascular endothelial growth factor VEGF and endostatin in patients with active diabetic retinopathy DR or quiescent DR. In the vitreous fluid of active DR, the concentration of VEGF was high, but the concentration of endostatin was low thick line.

On the other hand, in the vitreous fluid of quiescent DR, the concentration of VEGF was low but the concentration of endostatin was high thin line. Correlation between the concentrations of vascular endothelial growth factor VEGF and endostatin.

Noma H , Funatsu H , Yamashita H , Kitano S , Mishima HK , Hori S. Regulation of Angiogenesis in Diabetic Retinopathy : Possible Balance Between Vascular Endothelial Growth Factor and Endostatin. Arch Ophthalmol. From the Departments of Ophthalmology, Diabetes Center, Tokyo Women's Medical University, Tokyo Drs Noma, Funatsu, and Kitano , Hiroshima University Medical School, Hiroshima Drs Noma and Mishima , and Yamagata University Medical School, Yamagata Dr Yamashita , and Tokyo Women's Medical University Dr Hori , Japan.

Objective To investigate the mechanisms of regulation between vascular endothelial growth factor VEGF as a stimulator and endostatin as an inhibitor of angiogenesis in diabetic retinopathy DR.

Methods One hundred fifty-nine eyes of diabetic patients were studied. Concentrations of VEGF and endostatin in vitreous fluid and aqueous humor, obtained from the eyes during ocular surgery, were measured by enzyme-linked immunosorbent assay. The severity of DR was quantified according to the Early Treatment Diabetic Retinopathy Study retinopathy severity scale; fundus findings, including soft exudates, intraretinal microvascular abnormalities, venous abnormalities, new vessels elsewhere, new vessels on the disc, vitreous hemorrhage, and retinal detachment, were graded and evaluated.

Concentrations of VEGF and endostatin in plasma were also measured by enzyme-linked immunosorbent assay. Main Outcome Measures Concentrations of VEGF and endostatin in vitreous fluid and plasma. The correlations among the clinical records and the levels of VEGF and endostatin were analyzed statistically.

The concentrations of VEGF and endostatin in the eyes were not correlated with those in the plasma. Conclusions These results show that both VEGF and endostatin are correlated with angiogenesis in DR. Our study suggests that the regulation mechanism between VEGF and endostatin is associated with the activity of DR and may be a good candidate to develop useful therapeutic agents for proliferative DR.

NEW VESSEL formation in diabetic retinopathy DR causes visual loss with vitreous hemorrhage, retinal detachment, and neovascular glaucoma. Various cytokines and growth factors are considered to be involved in these processes and the pathogenesis of angiogenesis.

It is hypothesized that the net balance between angiogenic stimulators and inhibitors regulates the switching of the angiogenic process.

Vascular endothelial growth factor VEGF acts as an endothelial cell mitogen 9 , 10 in vitro and induces increased vascular permeability 11 and angiogenesis in vivo. Intraocular VEGF concentrations are increased during the periods of active intraocular neovascularization in patients with proliferative DR.

Many endogenous inhibitors of angiogenesis, including endostatin, 13 thrombospondin, 14 , 15 interferon α and β, prolactin, platelet factor 4, 16 - 18 and angiostatin, 19 have been reported. Endostatin is an angiogenic inhibitor produced by hemangioendothelioma. In the present study, we examined the regulation mechanism between VEGF as an angiogenic stimulator and endostatin as an angiogenic inhibitor in DR and showed that endostatin may be related to angiogenesis activity in cooperating with VEGF in DR.

Samples of aqueous humor and vitreous fluid were obtained from eyes of diabetic patients whose mean SD age was The patients included 77 men and 43 women. The mean SD duration of diabetes mellitus was Patients were excluded if they had undergone previous intraocular surgery or had a history of branch retinal vein occlusion and uveitis.

All procedures conformed to the Declaration of Helsinki for research involving human subjects. Ethics committee approval was obtained, and all participants gave informed consent.

The activity of DR is classified into active and quiescent. If there are extensive changes, including active neovascularization and proliferative membrane, fresh vitreous hemorrhage, and progressive retinal detachment, it is classified as active.

If it becomes silent on photocoagulation, even with remaining neovascularization and proliferative membrane, it is classified as quiescent. The results ensured that the levels of factors in intraocular fluid and plasma samples were within the detectable range using these assays.

The minimum detectable concentrations sensitivity using the assay kits were The preoperative and operative findings were recorded. Clinical data, including the severity of DR, were obtained by the surgeon using standardized forms at the time of surgery and were confirmed by standardized fundus color photography and fluorescein angiography performed within 3 days after the operation.

The severity of DR was graded according to the modified Early Treatment Diabetic Retinopathy Study ETDRS retinopathy severity scale. Results are presented as mean ± SD or geometric mean ± SD for data shown on the logarithmic scale.

To determine the relationship between angiogenic factors and the ETDRS retinopathy severity, Spearman rank-order correlation coefficient was applied. To test the heterogeneity of slopes of 2 linear regression lines, analysis of covariance with interaction was used.

In this model, variables were analyzed on the logarithmic scale because of skewed distribution. Two-tailed P values of less than. The concentrations of VEGF in the aqueous humor geometric mean, The concentrations of endostatin in the aqueous humor mean, 2.

The concentration of VEGF in vitreous fluid was significantly correlated with the grades of soft exudate, IRMA, venous beading, venous loops, NVE, NVD, FPE, and vitreous hemorrhage Table 1.

The concentration of endostatin in vitreous fluid was significantly correlated with the grades of NVE, FPE, and retinal detachment Table 1. The VEGF levels were higher in the vitreous fluid of active DR than in the vitreous fluid of quiescent DR. The endostatin levels were lower in the vitreous fluid of active DR than in the vitreous fluid of quiescent DR.

On the other hand, in the vitreous fluid of quiescent DR, the concentration of VEGF was low but the concentration of endostatin was high. There was no significant correlation between the plasma concentration of VEGF or endostatin and the severity of DR data not shown.

The concentration of VEGF in neither the aqueous humor As for endostatin, no significant relationship was found between its concentration in aqueous humor 2. We obtained the following findings in this study. First, in patients with DR, endostatin was detected in aqueous humor and vitreous fluid.

Second, the endostatin and VEGF concentrations in aqueous humor and vitreous fluid were correlated with the severity of DR. Third, some of the patients with severe DR showed a high endostatin concentration in vitreous fluid, but others showed a low concentration. Fourth, the slope of the regression line between the VEGF and endostatin concentrations in vitreous fluid differed significantly between active DR and quiescent DR.

There was a significant positive correlation between the severity of DR and the VEGF concentration in the aqueous humor and vitreous fluid in the present study. These results were consistent with the findings of previous reports. These results suggest that VEGF stimulates angiogenesis in the pathology of DR.

Our results and the previous reports suggest that VEGF is associated with enhanced vascular permeability, vascular occlusion, and angiogenesis.

The severity of DR was also positively correlated with the endostatin concentrations in both aqueous humor and vitreous fluid. Of the fundus findings, the grades of NVE, FPE, and retinal detachment were positively correlated with the endostatin concentration in vitreous fluid Table 1.

In the aqueous humor and vitreous fluid, the VEGF concentration was positively correlated with the endostatin concentration.

These results suggest that endostatin expression is correlated with VEGF expression. We measured blood pressure, proteinuria and pups development. In both models, eye fundal exploration and immunoblot for VEGF, PEDF, P RR and AT1R were performed.

We found that the development of hypertension occurred faster in previously PE rats than in normal animals. VEGF, PEDF, P RR and AT1R were increased in PE, but in L-NAME-induced hypertension only P RR and AT1R were altered.

Eye fundal data indicated that PE induced a level I retinopathy, but L-NAME induced a faster and more severe retinopathy in previously PE animals compared to previously normal pregnancy rats.

Virtual energy refuel angiogenesis of the Anyiogenesis is a Angiogfnesis component Brown rice and beans irreversible causes of retinopathu, as eetinopathy in Natural energy snacks diabetic retinopathy PDR. The pathogenesis of PDR is complex and involves vascular, inflammatory, and neuronal mechanisms. Several structural and molecular alterations associated to PDR are related to the presence of inflammation that appears to play a non-redundant role in the neovascular response that characterizes the retina of PDR patients. Vascular endothelial growth factor VEGF blockers have evolved over time for the treatment of retinal neovascularization. However, several limitations to anti-VEGF interventions exist. Angiogenesis and hypertensive retinopathy GeorgiadisStamatina A. KabanarouGeorgios BatsosElias FeretisTina Virtual energy refuel Bilateral Effective visceral weight loss Retinopathy Hypertenaive with Retinal Neovascularization: Panretinal Hypertensife or Intravitreal Anti-VEGF Treatment. Case Rep Brown rice and beans 1 Hjpertensive ; 5 2 : — Purpose: To present the case of a patient with bilateral hypertensive retinopathy complicated with retinal neovascularization who received anti-VEGF intravitreal injection in one eye and panretinal photocoagulation PRP in the fellow eye. Methods: A year-old male patient presented with gradual visual loss in both eyes for the last 5 months. At that time, he was examined by an ophthalmologist and occlusive retinopathy due to malignant systematic hypertension was diagnosed.

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Retinopathy in Malignant Hypertension.

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