The vascularization paradox of non-union formation
AbstractDespite major research efforts to elucidate mechanisms of non-union formation, failed fracture healing remains a common complication in orthopedic surgery. Adequate vascularization has been recognized as a crucial factor for successful bone regeneration, as newly formed microvessels guarantee the supply of the callus tissue with vital oxygen, nutrients, and growth factors. Accordingly, a vast number of preclinical studies have focused on the development of vascularization strategies to stimulate fracture repair. However, recent evidence suggests that stimulation of blood vessel formation is an oversimplified approa...
Source: Angiogenesis - February 14, 2022 Category: Molecular Biology Source Type: research
Identification of vascular cues contributing to cancer cell stemness and function
AbstractGlioblastoma stem cells (GSCs) reside close to blood vessels (BVs) but vascular cues contributing to GSC stemness and the nature of GSC-BVs cross talk are not fully understood. Here, we dissected vascular cues influencing GSC gene expression and function to perfusion-based vascular cues, as well as to those requiring direct GSC-endothelial cell (EC) contacts. In light of our previous finding that perivascular tumor cells are metabolically different from tumor cells residing further downstream, cancer cells residing within a narrow, < 60 µm wide perivascular niche were isolated and confirmed to possess a ...
Source: Angiogenesis - February 3, 2022 Category: Molecular Biology Source Type: research
Plasma levels of angiopoietin-2, VEGF-A, and VCAM-1 as markers of bevacizumab-induced hypertension: CALGB 80303 and 90401 (Alliance)
This study aimed to identify plasma proteins related to the function of the vasculature to predict the risk of severe bevacizumab-induced hypertension. Using pretreated plasma samples from 398 bevacizumab-treated patients in two clinical trials (CALGB 80303 and 90401), the levels of 17 proteins were measured via ELISA. The association between proteins and grade 3 bevacizumab-induced hypertension was performed by calculating the odds ratio (OR) from logistic regression adjusting for age, sex, and clinical trial. Using the optimal cut-point of each protein, sensitivity, specificity, positive predictive value (PPV), and negat...
Source: Angiogenesis - February 1, 2022 Category: Molecular Biology Source Type: research
The HGR motif is the antiangiogenic determinant of vasoinhibin: implications for a therapeutic orally active oligopeptide
AbstractThe hormone prolactin acquires antiangiogenic and antivasopermeability properties after undergoing proteolytic cleavage to vasoinhibin, an endogenous prolactin fragment of 123 or more amino acids that inhibits the action of multiple proangiogenic factors. Preclinical and clinical evidence supports the therapeutic potential of vasoinhibin against angiogenesis-related diseases including diabetic retinopathy, peripartum cardiomyopathy, rheumatoid arthritis, and cancer. However, the use of vasoinhibin in the clinic has been limited by difficulties in its production. Here, we removed this barrier to using vasoinhibin as...
Source: Angiogenesis - February 1, 2022 Category: Molecular Biology Source Type: research
Angiopoietin-2-induced lymphatic endothelial cell migration drives lymphangiogenesis via the β1 integrin-RhoA-formin axis
This study shows that Ang2-driven human dermal lymphatic endothelial cell migration depends on RhoA. We demonstrate that Ang2-induced migration is independent of the Tie receptors, but dependent on β1 integrin-mediated RhoA activation with knockdown, pharmacological approaches, and protein sequencing experiments. Although the key proteins downstream of RhoA, Rho kinase (ROCK) and myosin light chain, were activated, blockade of ROCK did not abrogate the Ang2-driven migratory effect. However, f ormins, an alternative target of RhoA, were identified as key players, and especially FHOD1. The Ang2-RhoA relationship was explore...
Source: Angiogenesis - February 1, 2022 Category: Molecular Biology Source Type: research
Pazopanib for severe bleeding and transfusion-dependent anemia in hereditary hemorrhagic telangiectasia
In conclusion, pazopanib was safe and effective to manage severe bleeding in HHT, liberating all patient s from transfusion dependence and normalizing hematologic parameters at doses lower than used to treat malignancies. These findings require confirmation in a randomized trial. (Source: Angiogenesis)
Source: Angiogenesis - February 1, 2022 Category: Molecular Biology Source Type: research
Extracellular matrix stiffness controls VEGF165 secretion and neuroblastoma angiogenesis via the YAP/RUNX2/SRSF1 axis
AbstractAberrant variations in angiogenesis have been observed in tumor tissues with abnormal stiffness of extracellular matrix (ECM). However, it remains largely unclear how ECM stiffness influences tumor angiogenesis. Numerous studies have reported that vascular endothelial growth factor-A (VEGF-A) released from tumor cells plays crucial roles in angiogenesis. Hence, we demonstrated the role of ECM stiffness in VEGF-A release from neuroblastoma (NB) cells and the underlying mechanisms. Based on 17 NB clinical samples, a negative correlation was observed between the length of blood vessels and stiffness of NB tissues. In ...
Source: Angiogenesis - February 1, 2022 Category: Molecular Biology Source Type: research
Pazopanib for severe bleeding and transfusion-dependent anemia in hereditary hemorrhagic telangiectasia
In conclusion, pazopanib was safe and effective to manage severe bleeding in HHT, liberating all patient s from transfusion dependence and normalizing hematologic parameters at doses lower than used to treat malignancies. These findings require confirmation in a randomized trial. (Source: Angiogenesis)
Source: Angiogenesis - February 1, 2022 Category: Molecular Biology Source Type: research
Angiopoietin-2-induced lymphatic endothelial cell migration drives lymphangiogenesis via the β1 integrin-RhoA-formin axis
This study shows that Ang2-driven human dermal lymphatic endothelial cell migration depends on RhoA. We demonstrate that Ang2-induced migration is independent of the Tie receptors, but dependent on β1 integrin-mediated RhoA activation with knockdown, pharmacological approaches, and protein sequencing experiments. Although the key proteins downstream of RhoA, Rho kinase (ROCK) and myosin light chain, were activated, blockade of ROCK did not abrogate the Ang2-driven migratory effect. However, f ormins, an alternative target of RhoA, were identified as key players, and especially FHOD1. The Ang2-RhoA relationship was explore...
Source: Angiogenesis - February 1, 2022 Category: Molecular Biology Source Type: research
Deletion of endothelial α-parvin inhibits tumour angiogenesis, reduces tumour growth and induces tumour cell apoptosis
AbstractAlpha-parvin ( α-pv), an adaptor protein that mediates integrin-dependent cell–matrix interactions, is essential for endothelial cells migration and proliferation and is a key player in physiological angiogenesis. The role of α-pv in pathological angiogenesis is unknown. Here we demonstrate that endothelial α -pv is required for tumour angiogenesis. Using an inducible knockout approach in which the α-pv gene (Parva) was inactivated specifically in endothelial cells of brain tumour-bearing mice, we show that loss of endothelial α-pv results in reduced vessel density and decreased vascular complexity of the pa...
Source: Angiogenesis - January 31, 2022 Category: Molecular Biology Source Type: research
Copper stress impairs angiogenesis and lymphangiogenesis during zebrafish embryogenesis by down-regulating pERK1/2-foxm1-MMP2/9 axis and epigenetically regulating ccbe1 expression
In this study, we unveiled that intersegmental blood circulation was partially blocked in Cu2+-stressed zebrafish embryos and cell migration and tube formation were impaired in Cu2+-stressed mammalian HUVECs. Specifically, Cu2+-stressed embryos showed down-regulation in the expression ofamotl2 and its downstream pERK1/2-foxm1-MMP2/9 regulatory axis, and knockdown/knockout offoxm1 in zebrafish embryos phenocopied angiogenesis defects, whileFOXM1 knockdown HUVECs phenocopied cell migration and tube formation defects, indicating that excessive Cu2+-induced angiogenesis defects and blocked cell migration via down-regulatingamo...
Source: Angiogenesis - January 16, 2022 Category: Molecular Biology Source Type: research
