Identification of ILK as a critical regulator of VEGFR3 signalling and lymphatic vascular growth

Vascular endothelial growth factor receptor-3 (VEGFR3) signalling promotes lymphangiogenesis. While there are many reported mechanisms of VEGFR3 activation, there is little understanding of how VEGFR3 signalling is attenuated to prevent lymphatic vascular overgrowth and ensure proper lymph vessel development. Here, we show that endothelial cell-specific depletion of integrin-linked kinase (ILK) in mouse embryos hyper-activates VEGFR3 signalling and leads to overgrowth of the jugular lymph sacs/primordial thoracic ducts, oedema and embryonic lethality. Lymphatic endothelial cell (LEC)-specific deletion of Ilk in adult mice initiates lymphatic vascular expansion in different organs, including cornea, skin and myocardium. Knockdown of ILK in human LECs triggers VEGFR3 tyrosine phosphorylation and proliferation. ILK is further found to impede interactions between VEGFR3 and β1 integrin in vitro and in vivo, and endothelial cell-specific deletion of an Itgb1 allele rescues the excessive lymphatic vascular growth observed upon ILK depletion. Finally, mechanical stimulation disrupts the assembly of ILK and β1 integrin, releasing the integrin to enable its interaction with VEGFR3. Our data suggest that ILK facilitates mechanically regulated VEGFR3 signalling via controlling its interaction with β1 integrin and thus ensures proper development of lymphatic vessels

Vascular islands during microvascular regression and regrowth in adult networks

Objective: Angiogenesis is the growth of new vessels from pre-existing vessels and commonly associated with two modes: capillary sprouting and capillary splitting. Our previous work suggests vascular island incorporation might be another endothelial cell dynamic involved in microvascular remodeling. Vascular islands are defined as endothelial cell segments disconnected from nearby networks, and their origin remains unclear. The objective of this study was to determine whether vascular islands associated with microvascular regression are involved in network regrowth.Methods: Mesenteric tissues were harvested from adult male Wistar rats according to the experimental groups: unstimulated, post stimulation (10 and 70 days), and 70 days post stimulation + restimulation (3 and 10 days). Stimulation was induced by mast cell degranulation via intraperitoneal injections of compound 48/80. Tissues were immunolabeled for PECAM (endothelial cells), NG2 (pericytes), collagen IV (basement membrane), and BrdU (proliferation).Results: Vascular area per tissue area and length density increased by day 10 post stimulation compared to the unstimulated group. At day 70, vascular area and length density were then decreased, indicating vascular regression compared to day 10. The number of vascular islands at day 10 post stimulation was dramatically reduced compared to the unstimulated group. During regression at day 70, the number of islands increased. The disconnected endothelial cells were commonly bridged to surrounding networks by collagen IV labeling. NG2-positive pericytes were observed along both the islands and the collagen IV tracks. At 3 days post restimulation, vascular islands contained BrdU-positive cells. By day 10 post restimulation, the number of vascular islands was dramatically reduced.Conclusion: The results suggest that vascular islands originating during microvascular regression are capable of proliferation and incorporation into nearby networks during regrowth

Cell proliferation along vascular islands during microvascular network growth

<p>Abstract</p> <p>Background</p> <p>Observations in our laboratory provide evidence of vascular islands, defined as disconnected endothelial cell segments, in the adult microcirculation. The objective of this study was to determine if vascular islands are involved in angiogenesis during microvascular network growth.</p> <p>Results</p> <p>Mesenteric tissues, which allow visualization of entire microvascular networks at a single cell level, were harvested from unstimulated adult male Wistar rats and Wistar rats 3 and 10 days post angiogenesis stimulation by mast cell degranulation with compound 48/80. Tissues were immunolabeled for PECAM and BRDU. Identification of vessel lumens via injection of FITC-dextran confirmed that endothelial cell segments were disconnected from nearby patent networks. Stimulated networks displayed increases in vascular area, length density, and capillary sprouting. On day 3, the percentage of islands with at least one BRDU-positive cell increased compared to the unstimulated level and was equal to the percentage of capillary sprouts with at least one BRDU-positive cell. At day 10, the number of vascular islands per vascular area dramatically decreased compared to unstimulated and day 3 levels.</p> <p>Conclusions</p> <p>These results show that vascular islands have the ability to proliferate and suggest that they are able to incorporate into the microcirculation during the initial stages of microvascular network growth.</p

Seniors | Class of \u2712

PLEASE NOTE: Where applicable, the audio has been removed from this file due to copyrighted material. The garments shown here represent the Senior Class of \u2712. The garments were created in response to the following design challenges: Concepts in Color Collection: design a collection based on an individual concept with a focus on color and texture. Senior Thesis Collection: create a collection that reflects the essence and philosophies of your personal vision

Five Design Challenges

PLEASE NOTE: Where applicable, the audio has been removed from this file due to copyrighted material. The garments shown here represent the Classes of \u2713, \u2712 and \u2711 . The garments were created in response to the following five design challenges: Sophomores, Class of \u2713: Re-Innovative Design: explore the properties of recycled materials other than fabric while creating a wearable piece. Print Design Project create a garment that makes optimal use of printed fabric designed by a RISD Textiles student. Juniors, Class of \u2712: Knitwear Design: explore the properties of knits and design cut-and-sew and machine-knit garments. Tailoring Project: interpret traditional tailoring techniques to create a look with a jacket. Seniors, Class of \u2711: Cocktail Collection: design a collection of contemporary cocktail apparel in collaboration with the current RISD Museum exhibition Cocktail Culture: Ritual and Invention in American Fashion, 1920-1980