scholarly journals Antiangiogenic Effect of Platelet P2Y12 Inhibitor in Ischemia-Induced Angiogenesis in Mice Hindlimb

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Xiaoli Wang ◽  
Huan Zhao ◽  
Naiquan Yang ◽  
Yue Jin ◽  
Jianguo Chen

Purpose. Postischemic inflammation induces angiogenesis, while platelet P2Y12 inhibitors can alleviate this inflammation. Therefore, we studied the potential effects of P2Y12 inhibitor, ticagrelor, on angiogenesis in a mouse model of hindlimb ischemia. Methods. Laser Doppler perfusion imaging and capillary density measurement were used for angiogenesis quantified. Immunofluorescence was used to detect the level of CD31. The mice muscle was harvested for enzyme-linked immunosorbent (ELISA) assay of interleukin- (IL) 10 activity and Western blot determination of vascular endothelial growth factor (VEGF) production. Results. Ischemic hindlimb angiogenesis was sharply decreased in IL-10+/+ mice than IL-10-/- mice. Ticagrelor inhibited angiogenesis and blood reperfusion recovery significantly elevated the levels of IL-10 and decreased the expression of VEGF in the IL-10+/+ mouse ischemic hindlimb, which were abolished in IL-10-deficient (IL-10–/–) C57BL/6J mice. Conclusion. The study underscores that the effect of ticagrelor antiangiogenic function is related with the higher IL-10 expression.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Sinem Tunçer ◽  
Rafig Gurbanov

AbstractObjectivesThe expression level of Vascular Endothelial Growth Factor (VEGF) is assumed as a prognostic marker for several tumor types, including colorectal cancer. Therefore, the determination of pre- and post-therapy levels of VEGF appears to have great value in the assessment of tumor prognosis. Enzyme-Linked Immunosorbent Assay (ELISA) is commonly used for the determination of serum or plasma VEGF levels, but the method is costly and time-consuming. In this study, we aimed to describe a rapid and cost-effective analysis method to discriminate VEGF overexpressing colorectal cancer-derived conditioned medium (CM).MethodsAttenuated Total Reflection (ATR)-Fourier Transform Infrared (FTIR) spectroscopy, combined with Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA), was used to differentiate VEGF overexpressing colorectal cancer cell line CM from CM obtained from the corresponding control cells which express and secrete relatively lower amount of VEGF.ResultsSamples belong to VEGF overexpressing colorectal cancer cells were clearly distinguished from the control group with very high PC scores as PC1 + PC2 = 96%. Besides, a 100% accurate distinction between these two groups was achieved by the LDA analysis.ConclusionsATR-FTIR spectroscopy combined with pattern recognition techniques was able to discriminate CM of VEGF overexpressing colorectal cancer cells with high efficiency and accuracy.



2013 ◽  
Vol 62 (18) ◽  
pp. C93
Author(s):  
Ahmet Kemal Filiz ◽  
Hakan Güneş ◽  
Ercan Özdemir ◽  
Handan Güneş ◽  
Mehmet Birhan Yılmaz


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yan Xiong ◽  
M Julia Scerbo ◽  
Anett Seelig ◽  
Francesco Volta ◽  
Nils O'Brien ◽  
...  

Islet vascularization is essential for intact islet function and glucose homeostasis. We have previously shown that primary cilia directly regulate insulin secretion. However, it remains unclear whether they are also implicated in islet vascularization. At eight weeks, murine Bbs4-/-islets show significantly lower intra-islet capillary density with enlarged diameters. Transplanted Bbs4-/- islets exhibit delayed re-vascularization and reduced vascular fenestration after engraftment, partially impairing vascular permeability and glucose delivery to β-cells. We identified primary cilia on endothelial cells as the underlying cause of this regulation, via the vascular endothelial growth factor-A (VEGF-A)/VEGF receptor 2 (VEGFR2) pathway. In vitro silencing of ciliary genes in endothelial cells disrupts VEGF-A/VEGFR2 internalization and downstream signaling. Consequently, key features of angiogenesis including proliferation and migration are attenuated in human BBS4 silenced endothelial cells. We conclude that endothelial cell primary cilia regulate islet vascularization and vascular barrier function via the VEGF-A/VEGFR2 signaling pathway.



Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Naila Mahmut ◽  
Caroline Kinnear ◽  
Megan Thompson ◽  
Patrick Shannon ◽  
David Chitayat ◽  
...  

The RV in hypoplastic left heart syndrome (HLHS) and Tetralogy of Fallot (TOF) is exposed to hypoxia and abnormal load which may lead to RV dysfunction despite surgical repair. The ability of hypoxia to upregulate angiogenic signaling in the RV is not known. We measured vascular endothelial growth factor (VEGF) mediated regulation of cardiac progenitors in the RV of patients with HLHS and TOF. Methods: RV myocardial samples were obtained from 6 pts with HLHS (age 0.96±1.5 yrs), 6 pts with TOF (age 3.5±6.3 yrs) and 9 age-matched controls with structurally normal hearts (age 0.16±0.3 yrs) at surgery/transplant/autopsy. The following were measured: VEGF, thymosin β-4 (recruits progenitors), Nkx2.5 (myocyte precursor), Flk-1 (smooth muscle progenitor), CD34 (endothelial progenitor), and von willebrand factor (vWf) (endothelial marker). Results: (i) VEGF and thymosin β-4 expression was lower in HLHS vs controls. This was associated with reduced cardiac progenitors and lower myocardial capillary density vs controls (0.14±0.01 vs 0.55±0.16, p<0.05). (ii) VEGF expression was preserved but thymosin β-4 was reduced in RV in TOF. This was associated with preserved myocyte progenitors but reduction in endothelial and smooth muscle lineages and reduced capillary density vs controls (0.13±0.03 vs 0.55±0.16, p<0.05) (Figure 1 ). Conclusion: Hypoxia fails to induce an angiogenic response in the RV in cyanotic heart lesions. This may be due to reduced VEGF (HLHS) or impaired coupling of VEGF to thymosin β-4 (TOF). This maladaptation may contribute to post-operative RV dysfunction and lower RV regenerative capacity in later life. Figure 1: Reduced capillary density (red) in HLHS and TOF





2002 ◽  
Vol 50 (7) ◽  
pp. 935-944 ◽  
Author(s):  
Emma Tham ◽  
Jianming Wang ◽  
Fredrik Piehl ◽  
Günther Weber

Angiogenesis is implicated in a variety of human pathologies and may also play a role in the progression of heart failure. We have studied the expression of members of the vascular endothelial growth factor (VEGF) and the angiopoietin families and their receptors in mice lacking the mitochondrial transcription factor A. These mice lack functional respiratory chain activity in their myocytes and develop dilated cardiomyopathy (DCM) postnatally. We studied the hearts of the knockout mice by in situ hybridization, Western blotting analysis, and immunohistochemistry. VEGF-A mRNA and protein levels were elevated in the myocardium of the knockouts. Levels of the hypoxia inducible transcription factor 1 alpha (HIF1α) and of glyceraldehyde-3-phosphate dehydrogenase transcripts were also increased, whereas those of angiopoietin−1 and −2 were reduced. Despite the striking upregulation of VEGF-A, there was no increase in capillary density in the knockout hearts. This study suggests that a disturbance in angiogenesis may contribute to the pathogenesis of DCM.







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