Vascular endothelial growth factor in diabetes induced early retinal abnormalities

Cukiernik, Mark; Hileeto, Denise; Evans, Terry; Mukherjee, Shankar; Downey, Dónal B.; Chakrabarti, Subrata

doi:10.1016/j.diabres.2004.02.002

Cited by 33 publications

(35 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data are consistent with published data from our group indicating that bosentan also partially prevented the development of proteinuria and renal structural injury in a similar animal model of late overt diabetic nephropathy (Ding et al, 2003). Prevention of VEGF increase by macitentan in the retina of diabetic rats indicates potential antiedema activity since VEGF increases vascular permeability and is involved in early stage of retinal damage in this model (Cukiernik et al, 2004). Our results are also in line with a previous study in the same animal model, using another dual ET receptor antagonist, SB209670 (Masuzawa et al, 2006).…”

Section: Discussionsupporting

confidence: 82%

“…Measurement of retinal VEGF content, as a surrogate for microvascular permeability, assessed the severity of diabetic retinopathy (Cukiernik et al, 2004). At the end of the 24-week study, the right eye was dissected, the eyeball was opened through the corneoscleral portion, and a 2 ϫ 2-mm area of retina above the optic nerve was cut, homogenized in phosphate buffer, and centrifuged at 12,000 rpm.…”

Section: In Vivo Pharmacologymentioning

confidence: 99%

See 1 more Smart Citation

Pharmacology of Macitentan, an Orally Active Tissue-Targeting Dual Endothelin Receptor Antagonist

Iglarz¹,

Binkert²,

Morrison³

et al. 2008

J Pharmacol Exp Ther

297

298

View full text Add to dashboard Cite

Macitentan, also called Actelion-1 or -6-(2-(5-bromopyrimidin-2-yloxy)ethoxy)-pyrimidin-4-yl]-NЈ-propylaminosulfonamide], is a new dual ET A / ET B endothelin (ET) receptor antagonist designed for tissue targeting. Selection of macitentan was based on inhibitory potency on both ET receptors and optimization of physicochemical properties to achieve high affinity for lipophilic milieu. In vivo, macitentan is metabolized into a major and pharmacologically active metabolite, ACT-132577. Macitentan and its metabolite antagonized the specific binding of ET-1 on membranes of cells overexpressing ET A and ET B receptors and blunted ET-1-induced calcium mobilization in various natural cell lines, with inhibitory constants within the nanomolar range. In functional assays, macitentan and ACT-132577 inhibited ET-1-induced contractions in isolated endothelium-denuded rat aorta (ET A receptors) and sarafotoxin S6c-induced contractions in isolated rat trachea (ET B receptors). In rats with pulmonary hypertension, macitentan prevented both the increase of pulmonary pressure and the right ventricle hypertrophy, and it markedly improved survival. In diabetic rats, chronic administration of macitentan decreased blood pressure and proteinuria and prevented end-organ damage (renal vascular hypertrophy and structural injury). In conclusion, macitentan, by its tissuetargeting properties and dual antagonism of ET receptors, protects against end-organ damage in diabetes and improves survival in pulmonary hypertensive rats. This profile makes macitentan a new agent to treat cardiovascular disorders associated with chronic tissue ET system activation.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: In Vivo Pharmacologymentioning

confidence: 99%

Pharmacology of Macitentan, an Orally Active Tissue-Targeting Dual Endothelin Receptor Antagonist

Iglarz¹,

Binkert²,

Morrison³

et al. 2008

J Pharmacol Exp Ther

297

298

View full text Add to dashboard Cite

show abstract

“…In the group with diabetes, mean HbA 1 c concentration was 9.21±2.17%, while the mean blood pressure values were 156/87 mmHg. Both parameters exceeded norms set by the American and European Diabetology Association [15,16] and the VIIth Hypertension Report criteria [17].…”

Section: Discussionmentioning

confidence: 98%

Assessment of selected adhesion molecule and proinflammatory cytokine levels in the vitreous body of patients with type 2 diabetes — role of the inflammatory–immune process in the pathogenesis of proliferative diabetic retinopathy

Adamiec-Mroczek

Oficjalska−Młyńczak

2008

Graefes Arch Clin Exp Ophthalmol

View full text Add to dashboard Cite

show abstract

“…On the other side, vascular endothelial growth factor (VEGF), one of the strongest hyperpermeability inducers (Senger et al 1990), plays a critical role in both physiological and pathological hyperpermeability (Bates and Harper 2002). Overexpression of VEGF was found in the progression of nephritic and ophthalmic complications in diabetes (Kim et al 2000;Cukiernik et al 2004). The molecular mechanism involved in the permeability alteration induced by VEGF in diabetic condition is not clear; however, there are evidences indicating that caveolae was indispensable to the process, and it was suggested that VEGF-induced permeability was mediated by caveolae (Feng et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

Tian

Zhang

et al. 2012

Genes Nutr

View full text Add to dashboard Cite

Endothelial hyperpermeability induced by hyperglycemia is the initial step in the development of atherosclerosis, one of the most serious cardiovascular complications in diabetes. In the present study, we investigated the effects of resveratrol (RSV), a bioactive ingredient extracted from Chinese herb rhizoma polygonum cuspidatum, on permeability in vitro and the molecular mechanisms involved. Permeability was assessed by the efflux of fluorescein isothiocyanate (FITC)-dextran permeated through the monolayer endothelial cells (ECs). The mRNA levels, protein expressions, and secretions were measured by quantitative real-time PCR, western blot, and ELISA, respectively. Increased permeability and caveolin-1 (cav-1) expression were observed in monolayer ECs exposed to high glucose. Resveratrol treatment alleviated the hyperpermeability and the overexpression of cav-1 induced by high glucose in a dose-dependent manner. b-Cyclodextrin, a structural inhibitor of caveolae, reduced the hyperpermeability caused by high glucose. Resveratrol also down-regulated the increased expressions of vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR, or VEGF receptor-2) induced by high glucose. Inhibition of VEGF/KDR pathway by using SU5416, a selective inhibitor of KDR, alleviated the hyperpermeability and the cav-1 overexpression induced by high glucose. The above results demonstrate that RSV ameliorates caveolae-mediated hyperpermeability induced by high glucose via VEGF/KDR pathway.

show abstract

Vascular endothelial growth factor in diabetes induced early retinal abnormalities

Cited by 33 publications

References 38 publications

Pharmacology of Macitentan, an Orally Active Tissue-Targeting Dual Endothelin Receptor Antagonist

Pharmacology of Macitentan, an Orally Active Tissue-Targeting Dual Endothelin Receptor Antagonist

Assessment of selected adhesion molecule and proinflammatory cytokine levels in the vitreous body of patients with type 2 diabetes — role of the inflammatory–immune process in the pathogenesis of proliferative diabetic retinopathy

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

Contact Info

Product

Resources

About