Vascular tumours and malformation
Brice Antao, S Irish Michael, Anthony Lander, S Rothenberg MD Steven in Succeeding in Paediatric Surgery Examinations, 2017
RASA1 mutations cause capillary malformation–arteriovenous malformation; patients have cutaneous stains and arteriovenous malformations. PTEN mutations cause lipovascular hamartomas, atypical arteriovenous malformations without capillary stains as well as frontal bossing and penile freckling. VEGFR3 mutations can result in congenital lymphoedema. Mutations in TIE2 can cause sporadic venous malformations as well as hereditary cutaneomucosal lesions. FOXC2 mutations are responsible for lymphoedema–distichiasis syndrome; patients have congenital lymphoedema and a double row of eyelashes. Glomulin mutations cause glomuvenous malformations; lesions are small, bluish and painful. Endoglin mutations result in hereditary haemorrhagic telangiectasia. Mutations in KRIT1 are responsible for cerebral cavernous malformations. SOX18 mutations cause hypotrichosis–lymphoedema–telangiectasia syndrome.
Arteriovenous malformations: Evaluation and treatment
Peter Gloviczki, Michael C. Dalsing, Bo Eklöf, Fedor Lurie, Thomas W. Wakefield, Monika L. Gloviczki in Handbook of Venous and Lymphatic Disorders, 2017
Although further studies are required in order to better understand these mechanisms, identification of the causative genes in several defects has already allowed a more precise diagnosis. Some mutations have been found to be responsible for a number of rare inheritable vascular malformations, such as Osler–Weber–Rendu syndrome (hereditary hemorrhagic telangiectasia), blue rubber bleb nevus syndrome (Bean’s syndrome), RASA1 mutations, PTEN mutations, etc.24–27 For example, hereditary hemorrhagic telangiectasia is an autosomal dominant condition caused by loss-of-function mutations in the genes encoding activin receptor-like kinase-1 (ACVRL1) and endoglin (ENG), both transforming growth factor-β vascular growth factors.
Hemangiomas and vascular malformations
Prem Puri in Newborn Surgery, 2017
AVM results from an error in vascular development during embryogenesis. An absent capillary bed causes shunting of blood directly from the arterial to venous circulation, through a fistula (direct connection of an artery to a vein) or nidus (abnormal channels bridging the feeding artery to the draining veins).71 Genetic abnormalities cause certain types of familial AVM. Hereditary hemorrhagic telangiectasia is due to mutations in endoglin and activin receptor-like kinase 1 (ALK-1), which affect transforming growth factor-beta (TGF-β) signaling.83 Capillary malformation–AVM (CM-AVM) results from a mutation in RASA1.84 Patients with PTEN mutations also can develop arteriovenous anomalies.85
Bone morphogenetic protein (BMP)9 in cancer development: mechanistic, diagnostic, and therapeutic approaches?
Published in Journal of Drug Targeting, 2023
Ali G. Alkhathami, Mustafa Ryadh Abdullah, Muhjaha Ahmed, Hanan Hassan Ahmed, Sarab W. Alwash, Zahra Muhammed Mahdi, Fahad Alsaikhan, Ayed A. Dera
Another study regarding the BMP9 neutralisation approach is based on endoglin. In endothelial cells and endothelial colony-forming cells, endoglin is predominantly expressed as a type I transmembrane glycoprotein. It is also known as an essential co-receptor for TGFβ, functioning an essential role in angiogenesis [75]. There is increasing evidence in which a cross-link between BMP9 and membrane-bound endoglin has been observed. Based on this observation it was designed a chimaera composed of endoglin extracellular domain ECD fused to Fc (EngECD-Fc) to assess its interaction with BMP9 to modulate its function. Data have shown that Endoglin ECD binds BMP9 selectively and strongly at physiological temperatures. In terms of biological activity, EngECD-Fc significantly decreased VEGF-induced vasculation and vessel formation in vivo chick chorioallantoic membrane assay. Moreover, murine EngECD-Fc functioned as an anti-angiogenic factor by reducing vessel sprouting in FGF/VEGF-induced tumour angiogenesis and decreased tumour burden in C26 colon carcinoma-bearing mice, highlighting the efficacy of EngECD-Fc as a potential anti-angiogenic agent [76].
Differential expression of miRNAs are associated with the insulin signaling pathway in preeclampsia and gestational hypertension
Published in Clinical and Experimental Hypertension, 2018
Olive P Khaliq, Saravanakumar Murugesan, Jagidesa Moodley, Irene Mackraj
In the current study, miRNA-29a was upregulated in the serum of preeclamptic and GH patients compared to the normotensives. Increased miRNA-29a expression has been reported to result in an up-regulation of PI3K and downregulation of AKT target genes in the insulin signaling pathway (22). This disrupts the insulin signaling pathway and contributes to the pathogenesis of PE. miRNA −29a has been reported to directly target the regulatory subunit found in PI3K known as p85α (22). According to Geering et al., (2007), upregulated miRNA −29a directly increases p85α expression, resulting in downregulation of the AKT protein. The physiological function of AKT is to regulate cellular metabolism through the insulin signaling pathway (40). In the present study, the western blot results showed that AKT is under-expressed in the placental tissue of preeclamptic patients compared to normotensives. These results are in keeping with that of Geering et al., (2007), Cudmore et al., (2011) and Pillar et al., (2015). It has been stated that loss of AKT activity increases the levels of soluble endoglin release (sEng), which in turn, increases the risk of PE (23). Soluble endoglin release inhibits angiogenic factors like the vascular endothelial growth factor (VEGF) (41). Vascular endothelial growth factor has been reported to induce a variety of proteins including PI3K and also regulate endothelial cell proliferation and cell differentiation via the PI3K/AKT signal transduction pathway (42).
Soluble endoglin in urine as an early-pregnancy preeclampsia marker: antenatal longitudinal feasibility study
Published in Journal of Obstetrics and Gynaecology, 2021
Zilma Silveira Nogueira Reis, Jacqueline Braga Pereira, Lúcia Aparecida C. Costa, Juliana Silva Barra
Angiogenesis factors, as well as their cellular receptors, have an established role in the regulation of placental vascular formation (Kar 2014). An imbalance in this equilibrium results in the loss of functional adjustment between vasodilator and vasoactive substances. In this process, the adjustment between anti-angiogenic and pro-angiogenic influences needs to occur for successful placentation (Kang et al. 2011). Endoglin is an anti-angiogenic glycoprotein expressed on endothelial cells and syncytiotrophoblasts whose elevated soluble circulating concentration in preeclampsia suggests its position as a diagnostic or prognostic marker for this disease (Cetin et al. 2011). Although the levels of soluble endoglin (sEng) and sFlt-1 are increased in the circulation of women with preeclampsia, their levels can differ with the sample type (Brownfoot et al. 2017). There are scarce reports regarding free urinary levels of sEng. When normalised to creatinine, such levels increase significantly during the clinical phase of severe preeclampsia (Buhimschi et al. 2010).
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