Endothelial alpha-parvin controls integrity of developing vasculature and is required for maintenance of cell-cell junctions

RATIONALE: Angiogenesis and vessel integrity depend on the adhesion of endothelial cells (EC) to the extracellular matrix (ECM) and to adjacent ECs. The focal adhesion protein alpha-parvin (alpha-pv) is essential for vascular development. However, the role of alpha-pv in ECs in vivo is not known. OBJECTIVE: To determine the function of alpha-pv in ECs during vascular development in vivo and the underlying mechanisms. METHODS AND RESULTS: We deleted the alpha-pv gene specifically in ECs of mice to study its role in angiogenesis and vascular development. Here we show that endothelial-specific deletion of alpha-pv in mice results in late embryonic lethality associated with hemorrhages and reduced vascular density. Postnatal induced EC-specific deletion of alpha-pv leads to retinal hypovascularization due to reduced vessel sprouting and excessive vessel regression. In the absence of alpha-pv, blood vessels display impaired VE-cadherin junction morphology. In vitro, alpha-pv deficient ECs show reduced stable adherens junctions, decreased monolayer formation and impaired motility, associated with reduced formation of integrin-mediated cell-ECM adhesion structures and an altered actin cytoskeleton. CONCLUSIONS: Endothelial alpha-pv is essential for vessel sprouting and for vessel stability

Shear stress switches the association of endothelial enhancers from ETV/ETS to KLF transcription factor binding sites.

Endothelial cells (ECs) lining blood vessels are exposed to mechanical forces, such as shear stress. These forces control many aspects of EC biology, including vascular tone, cell migration and proliferation. Despite a good understanding of the genes responding to shear stress, our insight into the transcriptional regulation of these genes is much more limited. Here, we set out to study alterations in the chromatin landscape of human umbilical vein endothelial cells (HUVEC) exposed to laminar shear stress. To do so, we performed ChIP-Seq for H3K27 acetylation, indicative of active enhancer elements and ATAC-Seq to mark regions of open chromatin in addition to RNA-Seq on HUVEC exposed to 6 h of laminar shear stress. Our results show a correlation of gained and lost enhancers with up and downregulated genes, respectively. DNA motif analysis revealed an over-representation of KLF transcription factor (TF) binding sites in gained enhancers, while lost enhancers contained more ETV/ETS motifs. We validated a subset of flow responsive enhancers using luciferase-based reporter constructs and CRISPR-Cas9 mediated genome editing. Lastly, we characterized the shear stress response in ECs of zebrafish embryos using RNA-Seq. Our results lay the groundwork for the exploration of shear stress responsive elements in controlling EC biology

Platelet Rich Plasma: Quantification of growth factor levels and the effect on growth and differentiation of rat bone marrow cells.

Contains fulltext : 49701.pdf (publisher's version ) (Open Access

Meeting report from the 2nd International Symposium on New Frontiers in Cardiovascular Research. Protecting the cardiovascular system from ischemia: between bench and bedside

10.1007/s00395-015-0527-0Basic Research in Cardiology1111Jan-1

Dengue

Lecture 49 ISBN e-book : 9781615045754International audienc