Endothelial Rap1B mediates T-cell exclusion to promote tumor growth: a novel mechanism underlying vascular immunosuppression
AbstractOvercoming vascular immunosuppression: lack of endothelial cell (EC) responsiveness to inflammatory stimuli in the proangiogenic environment of tumors, is essential for successful cancer immunotherapy. The mechanisms through which Vascular Endothelial Growth Factor A(VEGF-A) modulates tumor EC response to exclude T-cells are not well understood. Here, we demonstrate that EC-specific deletion of small GTPase Rap1B, previously implicated in normal angiogenesis, restricts tumor growth in endothelial-specific Rap1B-knockout (Rap1BiΔEC) mice. EC-specific Rap1B deletion inhibits angiogenesis, but also leads to an altere...
Source: Angiogenesis - November 20, 2022 Category: Molecular Biology Source Type: research
Notch1 and Notch4 core binding domain peptibodies exhibit distinct ligand-binding and anti-angiogenic properties
AbstractThe Notch signaling pathway is an important therapeutic target for the treatment of inflammatory diseases and cancer. We previously created ligand-specific inhibitors of Notch signaling comprised of Fc fusions to specific EGF-like repeats of the Notch1 extracellular domain, called Notch decoys, which bound ligands, blocked Notch signaling, and showed anti-tumor activity with low toxicity. However, the study of their function depended on virally mediated expression, which precluded dosage control and limited clinical applicability. We have refined the decoy design to create peptibody-based Notch inhibitors comprisin...
Source: Angiogenesis - November 15, 2022 Category: Molecular Biology Source Type: research
Inflammation and vascular remodeling in COVID-19 hearts
AbstractA wide range of cardiac symptoms have been observed in COVID-19 patients, often significantly influencing the clinical outcome. While the pathophysiology of pulmonary COVID-19 manifestation has been substantially unraveled, the underlying pathomechanisms of cardiac involvement in COVID-19 are largely unknown. In this multicentre study, we performed a comprehensive analysis of heart samples from 24 autopsies with confirmed SARS-CoV-2 infection and compared them to samples of age-matched Influenza H1N1 A (n = 16), lymphocytic non-influenza myocarditis cases (n = 8), and non-inflamed heart tissue (n = 9). ...
Source: Angiogenesis - November 12, 2022 Category: Molecular Biology Source Type: research
BMP10 functions independently from BMP9 for the development of a proper arteriovenous network
We examined whether globalBmp10-inducible knockout (iKO) mice develop AVMs at neonatal and adult stages in comparison with control,Bmp9-KO, andBmp9/10-double KO (dKO) mice.Bmp10-iKO andBmp9/10-dKO mice showed AVMs in developing retina, postnatal brain, and adult wounded skin, whileBmp9-KO did not display any noticeable vascular defects.Bmp10 deficiency resulted in increased proliferation and size of endothelial cells in AVM vessels. The impaired neurovascular integrity in the brain and retina ofBmp10-iKO andBmp9/10-dKO mice was detected.Bmp9/10-dKO mice exhibited the lethality and vascular malformation similar toBmp10-iKO ...
Source: Angiogenesis - November 8, 2022 Category: Molecular Biology Source Type: research
Tissue-resident glial cells associate with tumoral vasculature and promote cancer progression
AbstractCancer cells are embedded within the tissue and interact dynamically with its components during cancer progression. Understanding the contribution of cellular components within the tumor microenvironment is crucial for the success of therapeutic applications. Here, we reveal the presence of perivascular GFAP+/Plp1+ cells within the tumor microenvironment. Using in vivo inducible Cre/loxP mediated systems, we demonstrated that these cells derive from tissue-resident Schwann cells. Genetic ablation of endogenous Schwann cells slowed down tumor growth and angiogenesis. Schwann cell-specific depletion also induced a bo...
Source: Angiogenesis - October 1, 2022 Category: Molecular Biology Source Type: research
Correction: RNA m6A methylation promotes the formation of vasculogenic mimicry in hepatocellular carcinoma via Hippo pathway
(Source: Angiogenesis)
Source: Angiogenesis - September 30, 2022 Category: Molecular Biology Source Type: research
Correction: Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats
(Source: Angiogenesis)
Source: Angiogenesis - September 10, 2022 Category: Molecular Biology Source Type: research
Correction: A novel lymphatic pattern promotes metastasis of cervical cancer in a hypoxic tumour-associated macrophage-dependent manner
(Source: Angiogenesis)
Source: Angiogenesis - September 10, 2022 Category: Molecular Biology Source Type: research
Correction: Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats
(Source: Angiogenesis)
Source: Angiogenesis - September 10, 2022 Category: Molecular Biology Source Type: research
