Search

Venous malformations (VMs) are slow-flow malformations of the venous vasculature and are the most common type of vascular malformation with a prevalence of 1%. Germline and somatic mutations have been shown to contribute to VM pathogenesis, but how these mutations affect VM pathobiology is not well understood. The goal of this study was to characterize VM endothelial and mural cell expression by performing a comprehensive expression analysis of VM vasculature. VM specimens (n = 16) were stained for pan-endothelial, arterial, venous, and endothelial progenitor cell proteins; proliferation was assessed with KI67. Endothelial cells in the VM vessels were abnormally orientated and improperly specified, as seen by the misexpression of both arterial and endothelial cell progenitor proteins not observed in control vessels. Consistent with arterialization of the endothelial cells, VM vessels were often surrounded by multiple layers of disorganized mural cells. VM endothelium also had a significant increase in proliferative endothelial cells, which may contribute to the dilated channels seen in VMs. Together the expression analysis indicates that the VM endothelium is misspecified and hyperproliferative, suggesting that VMs are biologically active lesions, consistent with clinical observations of VM progression over time.

Past experiences have a considerable impact on the success of future interactions across the animal kingdom. Known as winner and loser effects, victors of prior contests tend to have an increased chance of future success while losers are likely to experience additional failure. These effects are in part due to differential endocrine responses among competitors following initial bouts, with winners benefiting from subsequent increases in testosterone (T) and losers being disadvantaged by reductions in T and heightened stress hormones. Now well documented across a range of human competitions, sporting events provide an ideal setting to explore this biological phenomenon. This study uses the perspective of winner and loser effects to study the pattern of outcomes observed in consecutive baseball and softball games played in the same day (i.e., doubleheaders) at the collegiate level. Using archival data from the National Collegiate Athletic Association (NCAA), we show that the distribution of winning and losing within these contests is not random. Consistent with a previous report on Major League Baseball (MLB), collegiate baseball and softball doubleheaders are more likely to be swept (i.e., one team winning both games) than split (i.e., each team winning and losing once), and the margin of victory in the first game was positive predictor of this outcome. While there were no differences between the strength of these effects between baseball and softball, both collegiate sports resulted in greater proportion of sweeps than in MLB. A residency effect was also observed, whereby victors of sweeps were more often the home team. This home field advantage was stronger for collegiate baseball compared to softball and the MLB. This report adds to a large comparative literature on winner and loser effects, and provides insight into the dynamics that modulate human performance in high-level athletic competition.

Infantile hemangioma (IH) is a vascular tumor that begins with rapid vascular proliferation shortly after birth, followed by vascular involution in early childhood. We have found that NOTCH3, a critical regulator of mural cell differentiation and maturation, is expressed in hemangioma stem cells (HemSCs), suggesting that NOTCH3 may function in HemSC-to–mural cell differentiation and pathological vessel stabilization. Here, we demonstrate that NOTCH3 is expressed in NG2+PDGFRβ+ perivascular HemSCs and CD31+GLUT1+ hemangioma endothelial cells (HemECs) in proliferating IHs and becomes mostly restricted to the αSMA+NG2loPDGFRβlo mural cells in involuting IHs. NOTCH3 knockdown in HemSCs inhibited in vitro mural cell differentiation and perturbed αSMA expression. In a mouse model of IH, NOTCH3 knockdown or systemic expression of the NOTCH3 inhibitor, NOTCH3 Decoy, significantly decreased IH blood flow, vessel caliber, and αSMA+ perivascular cell coverage. Thus, NOTCH3 is necessary for HemSC-to–mural cell differentiation, and adequate perivascular cell coverage of IH vessels is required for IH vessel stability.