Diversity Is in My Veins

Abstract

Summary Endothelial cells are a highly diverse group of cells which display distinct cellular responses to exogenous stimuli. While the aptly named Vascular Endothelial Growth Factor -A(VEGF-A) signaling pathway is hailed as the most important signaling input for endothelial cells, additional factors also participate in regulating diverse aspects of endothelial behaviors and functions. Given this heterogeneity, these additional factors appear to play a critical role in creating a custom-tailored environment to regulate behaviors and functions of distinct subgroups of endothelial cells. For instance, molecular cues that modulate morphogenesis of arterial vascular beds can be quite distinct from those that govern morphogenesis of venous vascular beds. Recently, we have found that Bone Morphogenetic Protein (BMP) signaling selectively promotes angiogenesis from venous vascular beds without eliciting similar responses from arterial vascular beds in zebrafish, indicating that BMP signaling functions as a context-dependent regulator during vascular morphogenesis. In this review, we will provide an overview of the molecular mechanisms that underlie pro-angiogenic effects of BMP signaling on venous vascular beds in the context of endothelial heterogeneity, and suggest a more comprehensive picture of the molecular mechanisms of vascular morphogenesis during development.

Induced Pluripotent Stem Cells to Model Human Fibrodysplasia Ossificans Progressiva

“…Inhibition of BMP receptor kinase activity by LDN-212854 during the vascular specification stage (from day 3 of hiPSC differentiation) did not rescue the impaired FOP hiPSC-EC phenotypes (unpublished data). BMPs are indispensable for the formation of mesoderm where ECs originate, but they may function as a context-dependent regulator in vascular morphogenesis ( Kim et al., 2014 ). In addition, a recent publication indicated activin A signals through the mutant ALK2 R206H to stimulate HO in FOP conditional-on knockin mice ( Hatsell et al., 2015 ).…”

Endothelial to Mesenchymal Transition Represents a Key Link in the Interaction between Inflammation and Endothelial Dysfunction

“…Endothelial cells line the inner wall of blood vessels and exhibit diverse subtypes ( 2 , 8 , 33 ). Different ECs have different structural and functional characteristics based on their exposure to distinct microenvironments ( 2 , 8 , 9 , 33 , 66 ). They are activated in response to inflammatory stimuli, with this activation resulting in the expression of adhesion molecules necessary for leukocyte binding ( 33 ).…”

LRP in Endothelial Cells

“…Endothelial cells are highly heterogeneous 1 and participate in angiogenesis, an integrated set of responses in which new blood vessels are formed from existing ones. During angiogenesis, endothelial cells exhibit increased migration and proliferation 2 and contribute to the reorganization of the extracellular matrix.…”