更新于：2024-11-01

BMPR2 x VEGF

更新于：2024-11-01

基本信息

关联

项与 BMPR2 x VEGF 相关的药物

VEGF-BMP2 gene therapy(Kazan Federal University)

靶点

BMPR2 x VEGF

作用机制

BMPR2激动剂 [+1]

在研机构

Kazan Federal University

原研机构

Kazan Federal University

在研适应症

骨折

非在研适应症-

最高研发阶段临床阶段不明

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 BMPR2 x VEGF 相关的临床结果

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100 项与 BMPR2 x VEGF 相关的转化医学

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0 项与 BMPR2 x VEGF 相关的专利（医药）

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项与 BMPR2 x VEGF 相关的文献（医药）

2024-06-01·Vascular Pharmacology

SEMA3G regulates BMP9 inhibition of VEGF-mediated migration and network formation in pulmonary endothelial cells

Article

作者: Mirza, Sarah L ; Hodgson, Joshua ; Upton, Paul D ; Gräf, Stefan ; Dunmore, Benjamin J ; Morrell, Nicholas W

AIMSBone morphogenetic protein-9 (BMP9) is critical for bone morphogenetic protein receptor type-2 (BMPR2) signalling in pulmonary vascular endothelial cells. Furthermore, human genetics studies support the central role of disrupted BMPR2 mediated BMP9 signalling in vascular endothelial cells in the initiation of pulmonary arterial hypertension (PAH). In addition, loss-of-function mutations in BMP9 have been identified in PAH patients. BMP9 is considered to play an important role in vascular homeostasis and quiescence.METHODS AND RESULTSWe identified a novel BMP9 target as the class-3 semaphorin, SEMA3G. Although originally identified as playing a role in neuronal development, class-3 semaphorins may have important roles in endothelial function. Here we show that BMP9 transcriptional regulation of SEMA3G occurs via ALK1 and the canonical Smad pathway, requiring both Smad1 and Smad5. Knockdown studies demonstrated redundancy between type-2 receptors in that BMPR2 and ACTR2A were compensatory. Increased SEMA3G expression by BMP9 was found to be regulated by the transcription factor, SOX17. Moreover, we observed that SEMA3G regulates VEGF signalling by inhibiting VEGFR2 phosphorylation and that VEGF, in contrast to BMP9, negatively regulated SEMA3G transcription. Functional endothelial cell assays of VEGF-mediated migration and network formation revealed that BMP9 inhibition of VEGF was abrogated by SEMA3G knockdown. Conversely, treatment with recombinant SEMA3G partially mimicked the inhibitory action of BMP9 in these assays.CONCLUSIONSThis study provides further evidence for the anti-angiogenic role of BMP9 in microvascular endothelial cells and these functions are mediated at least in part via SOX17 and SEMA3G induction.

2022-07-01·Jornal de Pediatria4区 · 医学

Possible association between a polymorphism of EPAS1 gene and persistent pulmonary hypertension of the newborn: a case-control study

4区 · 医学

ArticleOA

作者: Chaiyasung, Tassamonwan ; Nakwan, Narongsak ; Singkhamanan, Kamonnut ; Charalsawadi, Chariyawan ; Mahasirimongkol, Surakameth ; Kunhapan, Punna ; Charoenlap, Cheep ; Satproedprai, Nusara

OBJECTIVETo explore possible genes related to the development of persistent pulmonary hypertension of the newborn (PPHN).METHODSThe authors identified 285 single nucleotide polymorphisms (SNPs) of 11 candidate genes (BMPR2, EPAS1, PDE3A, VEGFA, ENG, NOTCH3, SOD3, CPS1, ABCA3, ACVRL1, and SMAD9), using an Illumina Asian Screening Array-24 v1.0 BeadChip Array. The FastLmmC and R package was used for statistical analyses. The chi-square test and Cochrane-Armitage trend test were used to compare the allele and genotype frequencies between the groups and to test the genetic models, respectively.RESULTSA total of 45 PPHN infants and 294 control subjects were analyzed. The most common cause of PPHN was meconium aspiration syndrome. Among the 285 SNPs, 17 SNPs from 6 candidate genes (BMPR2, EPAS1, PDE3A, VEGFA, ENG, and NOTCH3) were significantly associated with PPHN (P < 0.05). After using the Bonferroni correction (P < 0.00018), only the rs17034984 SNP located in intron 1 of the EPAS1 gene remained significantly different between the PPHN and control subjects (P = 0.00014). The frequency of the TC/TT genotype of rs17034984 in the gene with the dominant model was significant in the patients with PPHN (OR = 5.38, 95% CI: 2.15-13.49). The T allele frequency of rs17034984 in the gene showed a significant difference compared with the control subjects (OR = 4.89, 95% CI: 2.03-11.82).CONCLUSIONSThe present study suggests that the rs17034984 variant of EPAS1 gene is associated with PPHN.

2021-05-01·Physiological Reports

Intermittent hypoxia changes the interaction of the kinin–VEGF system and impairs myocardial angiogenesis in the hypertrophic heart

Article

作者: Tufik, Sergio ; Chagas, Jair R. ; Nogueira‐Pedro, Amanda ; Visniauskas, Bruna ; Perry, Juliana C. ; Gomes, Guiomar N. ; Paredes‐Gamero, Edgar J.

Intermittent hypoxia (IH) is a feature of obstructive sleep apnea (OSA), a condition highly associated with hypertension-related cardiovascular diseases. Repeated episodes of IH contribute to imbalance of angiogenic growth factors in the hypertrophic heart, which is key in the progression of cardiovascular complications. In particular, the interaction between vascular endothelial growth factor (VEGF) and the kallikrein-kinin system (KKS) is essential for promoting angiogenesis. However, researchers have yet to investigate experimental models of IH that reproduce OSA, myocardial angiogenesis, and expression of KKS components. We examined temporal changes in cardiac angiogenesis in a mouse IH model. Adult male C57BI/6 J mice were implanted with Matrigel plugs and subjected to IH for 1-5 weeks with subsequent weekly histological evaluation of vascularization. Expression of VEGF and KKS components was also evaluated. After 3 weeks, in vivo myocardial angiogenesis and capillary density were decreased, accompanied by a late increase of VEGF and its type 2 receptor. Furthermore, IH increased left ventricular myocardium expression of the B2 bradykinin receptor, while reducing mRNA levels of B1 receptor. These results suggest that in IH, an unexpected response of the VEGF and KKS systems could explain the reduced capillary density and impaired angiogenesis in the hypoxic heart, with potential implications in hypertrophic heart malfunction.