Intravitreal injection of anti-miRs against miR-142-3p reduces angiogenesis and microglia activation in a mouse model of laser-induced choroidal neovascularization.

Age-related macular degeneration (AMD) is a worldwide leading cause of blindness affecting individuals over 50 years old. The most aggressive form, wet AMD, is characterized by choroidal neovascularization (CNV) and inflammation involving microglia recruitment. By using a laser-induced CNV mouse model, we provide evidence for a key role played by miR-142-3p during CNV formation.

Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells.

Mechanical force is a determinant of Notch signalling but the mechanism of force detection and its coupling to Notch are unclear. We propose a role for Piezo1 channels, which are mechanically-activated non-selective cation channels. In cultured microvascular endothelial cells, Piezo1 channel activation by either shear stress or a chemical agonist Yoda1 activated a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), a Ca-regulated transmembrane sheddase that mediates S2 Notch1 cleavage.

Impaired SMAD1/5 Mechanotransduction and Cx37 (Connexin37) Expression Enable Pathological Vessel Enlargement and Shunting.

Objective: Impaired ALK1 (activin receptor-like kinase-1)/Endoglin/BMP9 (bone morphogenetic protein 9) signaling predisposes to arteriovenous malformations (AVMs). Activation of SMAD1/5 signaling can be enhanced by shear stress. In the genetic disease hereditary hemorrhagic telangiectasia, which is characterized by arteriovenous malformations, the affected receptors are those involved in the activation of mechanosensitive SMAD1/5 signaling.

Resistance to retinopathy development in obese, diabetic and hypertensive ZSF1 rats: an exciting model to identify protective genes.

Diabetic retinopathy (DR) is one of the major complications of diabetes, which eventually leads to blindness. Up to date, no animal model has yet shown all the co-morbidities often observed in DR patients. Here, we investigated whether obese 42 weeks old ZSF1 rat, which spontaneously develops diabetes, hypertension and obesity, would be a suitable model to study DR.

Shear Stress and VE-Cadherin.

Objective- Vascular fusion represents an important mechanism of vessel enlargement during development; however, its significance in postnatal vessel enlargement is still unknown. During fusion, 2 adjoining vessels merge to share 1 larger lumen. The aim of this research was to identify the molecular mechanism responsible for vascular fusion.

Erythro-myeloid progenitors can differentiate from endothelial cells and modulate embryonic vascular remodeling.

Erythro-myeloid progenitors (EMPs) were recently described to arise from the yolk sac endothelium, just prior to vascular remodeling, and are the source of adult/post-natal tissue resident macrophages. Questions remain, however, concerning whether EMPs differentiate directly from the endothelium or merely pass through. We provide the first evidence in vivo that EMPs can emerge directly from endothelial cells (ECs) and demonstrate a role for these cells in vascular development.

CXCL1 microspheres: a novel tool to stimulate arteriogenesis.

Context: After arterial occlusion, diametrical growth of pre-existing natural bypasses around the obstruction, i.e. arteriogenesis, is the body's main coping mechanism.

Arteriovenous malformations in hereditary haemorrhagic telangiectasia: looking beyond ALK1-NOTCH interactions.

Hereditary haemorrhagic telangiectasia (HHT) is characterized by the development of arteriovenous malformations--enlarged shunts allowing arterial flow to bypass capillaries and enter directly into veins. HHT is caused by mutations in ALK1 or Endoglin; however, the majority of arteriovenous malformations are idiopathic and arise spontaneously. Idiopathic arteriovenous malformations differ from those due to loss of ALK1 in terms of both location and disease progression.

Update on vascularization in tissue engineering.

Vascularization of engineered tissues is critical for success. Adequate and physiologically regulated blood supply is important for viability of the implanted tissue but even more important for the proper function of parenchymal cells, which is the desired clinical outcome for most applications in regenerative medicine. Several methods are being developed to stimulate revascularization of engineered tissue.

Cellular decisions in cardiac outflow tract and coronary development: an act by VEGF and NOTCH.

Congenital cardiac abnormalities are, due to their relatively high frequency and severe impact on quality of life, an important focus in cardiovascular research. Recently, various human studies have revealed a high coincidence of VEGF and NOTCH polymorphisms with cardiovascular outflow tract anomalies, such as bicuspid aortic valves and Tetralogy of Fallot, next to predisposition for cardiovascular pathologies, including atherosclerosis and aortic valve calcification. This genetic association between VEGF/NOTCH mutations and congenital cardiovascular defects in humans has been supported by substantial proof from animal models, revealing interaction of both pathways in cellular processes that are crucial for cardiac development.

Notch regulation of hematopoiesis, endothelial precursor cells, and blood vessel formation: orchestrating the vasculature.

The development of the vascular system begins with the formation of hemangioblastic cells, hemangioblasts, which organize in blood islands in the yolk sac. The hemangioblasts differentiate into hematopoietic and angioblastic cells. Subsequently, the hematopoietic line will generate blood cells, whereas the angioblastic cells will give rise to vascular endothelial cells (ECs).

Soluble Jagged-1 inhibits neointima formation by attenuating Notch-Herp2 signaling.

Objective: Notch has been implicated in neointima formation as reflected by increased Notch/Jagged expression on vascular injury and the promigratory effect of Notch signaling on smooth muscle cells. Soluble Jagged-1 (sJag1) has been shown to inhibit Notch signaling in vitro; however, its capacity to suppress neointima formation remains unknown.

Methods And Results: Balloon injury of rat carotid arteries induced Notch1, Notch3, and Jagged-1 expression at days 3 and 14 postinjury.

Feed-forward signaling by membrane-bound ligand receptor circuit: the case of NOTCH DELTA-like 4 ligand in endothelial cells.

The DELTA like-4 ligand (DLL4) belongs to the highly conserved NOTCH family and is specifically expressed in the endothelium. DLL4 regulates crucial processes in vascular growth, including endothelial cell (EC) sprouting and arterial specification. Its expression is increased by VEGF-A.

A disintegrin and metalloprotease 10 is a novel mediator of vascular endothelial growth factor-induced endothelial cell function in angiogenesis and is associated with atherosclerosis.

Objective: To elucidate the downstream mechanisms of vascular endothelial growth factor receptor 2 (VEGFR2), a key receptor in angiogenesis, which has been associated with atherosclerotic plaque growth and instability.

Methods And Results: By using a yeast-2-hybrid assay, we identified A Disintegrin And Metalloprotease 10 (ADAM10) as a novel binding partner of VEGFR2. ADAM10 is a metalloprotease with sheddase activity involved in cell migration; however, its exact function in endothelial cells (ECs), angiogenesis, and atherosclerosis is largely unknown.

Developmental coronary maturation is disturbed by aberrant cardiac vascular endothelial growth factor expression and Notch signalling.

Aims: Currently, many potential cardiac revascularization therapies target the vascular endothelial growth factor (VEGF) pathway, with variable success. Knowledge regarding the role of the VEGF/Notch/ephrinB2 cascade in (ab)normal coronary development will provide information on the subtle balance of VEGF signalling in coronary maturation and might enhance our therapeutic possibilities.

Methods And Results: The effect of VEGF isoforms on coronary development was explored in vivo using immunohistochemistry and RT-qPCR on Vegf120/120 mouse embryos solely expressing VEGF120.