The Interaction between the Renin-Angiotensin System and Vascular Endothelial Growth Factor in the Pathogenesis of Retinal Neovascularization in Diabetes

2001 ◽  
Vol 38 (6) ◽  
pp. 527-535 ◽  
Author(s):  
Jennifer L. Wilkinson-Berka ◽  
Darren J. Kelly ◽  
Richard E. Gilbert
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Renin Angiotensin System ◽  
Retinal Neovascularization ◽  
Vascular Endothelial ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Endothelial Growth Factor

Significance of polymorphic variants of the renin-angiotensin system, pro-oxidant-antioxidant system and vascular endothelial growth factor as genetic predictors of preeclampsia

2020 ◽  
pp. 76-78
Author(s):  
Л.В. Акуленко ◽  
Н.Ю. Сакварелидзе ◽  
С.Г. Цахилова
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Antioxidant System ◽  
Renin Angiotensin System ◽  
Vascular Endothelial ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Genetic Predictors ◽  
Polymorphic Variants ◽  
Endothelial Growth Factor

В поиске генетических факторов риска развития преэклампсии изучалась роль полиморфных вариантов ключевых генов ренин-ангиотензиновой системы, прооксидантно-антиоксидантной системы и фактора роста эндотелия сосудов, возможно, формирующих ее основные клинические проявления: повышение артериального давления, оксидативный стресс плаценты и эндотелиальную дисфункцию сосудов в системе кровообращения «мать-плацента-плод». Определены достоверные генетические предикторы этого осложнения беременности. In the search for genetic risk factors for preeclampsia, the role of polymorphic variants of key genes of the renin-angiotensin system, pro-oxidant-antioxidant system, and vascular endothelial growth factor was studied, possibly forming its main clinical manifestations: increased blood pressure, placental oxidative stress, and endothelial vascular dysfunction in the «mother-placenta-fetus» circulatory system. Reliable genetic predictors of this pregnancy complication have been determined.

scholarly journals Evogliptin, a dipeptidyl peptidase-4 inhibitor, attenuates pathological retinal angiogenesis by suppressing vascular endothelial growth factor-induced Arf6 activation

2020 ◽  
Vol 52 (10) ◽  
pp. 1744-1753
Author(s):  
Songyi Seo ◽  
Mi-Kyung Kim ◽  
Ryul-I Kim ◽  
Yeongju Yeo ◽  
Koung Li Kim ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Dipeptidyl Peptidase ◽  
Inhibitory Effect ◽  
Retinal Neovascularization ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Dipeptidyl Peptidase 4 ◽  
Endothelial Growth Factor

Abstract Dipeptidyl peptidase-4 (DPP-4) inhibitors are used for the treatment of type 2 diabetes mellitus (DM). Recent studies have shown that beyond their effect in lowing glucose, DPP-4 inhibitors mitigate DM-related microvascular complications, such as diabetic retinopathy. However, the mechanism by which pathological retinal neovascularization, a major clinical manifestation of diabetic retinopathy, is inhibited is unclear. This study sought to examine the effects of evogliptin, a potent DPP-4 inhibitor, on pathological retinal neovascularization in mice and elucidate the mechanism by which evogliptin inhibits angiogenesis mediated by vascular endothelial growth factor (VEGF), a key factor in the vascular pathogenesis of proliferative diabetic retinopathy (PDR). In a murine model of PDR, an intravitreal injection of evogliptin significantly suppressed aberrant retinal neovascularization. In human endothelial cells, evogliptin reduced VEGF-induced angiogenesis. Western blot analysis showed that evogliptin inhibited the phosphorylation of signaling molecules associated with VEGF-induced cell adhesion and migration. Moreover, evogliptin substantially inhibited the VEGF-induced activation of adenosine 5′-diphosphate ribosylation factor 6 (Arf6), a small guanosine 5′-triphosphatase (GTPase) that regulates VEGF receptor 2 signal transduction. Direct activation of Arf6 using a chemical inhibitor of Arf-directed GTPase-activating protein completely abrogated the inhibitory effect of evogliptin on VEGF-induced activation of the angiogenic signaling pathway, which suggests that evogliptin suppresses VEGF-induced angiogenesis by blocking Arf6 activation. Our results provide insights into the molecular mechanism of the direct inhibitory effect of the DPP-4 inhibitor evogliptin on pathological retinal neovascularization. In addition to its glucose-lowering effect, the antiangiogenic effect of evogliptin could also render it beneficial for individuals with PDR.

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