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Abstract A recently discovered but unexplored mechanism of angiogenesis regulation is cross-family binding between platelet-derived growth factors (PDGFs) and vascular endothelial growth factor receptors (VEGFRs), which suggests a novel therapy for addressing vascular dysregulation. This study elucidates the role of PDGFs in endothelial cell (EC) signaling and functions, focusing on VEGFR activation. Using human dermal microvascular ECs (HDMECs) with double knockout of PDGFRα/β and human brain microvascular ECs (HBMECs), we show three key findings: (1) PDGF-AA and -BB induced VEGFR1 phosphorylation, peaking at 2-fold increases at low concentrations (0.5 ng/mL), while PDGF-AB stimulated a 2-fold rise in VEGFR2 phosphorylation. (2) Downstream effectors PLCγ1, Akt, and FAK were activated by all three PDGFs at levels comparable to VEGF-A, achieving approximately 70% of VEGF-A’s effects. (3) PDGF-BB significantly enhanced EC proliferation (up to 240%) and migration (up to 170%), with lower PDGF concentrations (0.5–5 ng/mL) eliciting stronger effects than higher concentrations (50–100 ng/mL). Overall, PDGF subtypes differentially induce VEGFR phosphorylation, downstream effector activation, and angiogenic hallmarks such as proliferation and migration, revealing novel mechanisms for regulating endothelial function. 

Abstract PurposeReceptor tyrosine kinase (RTK) concentrations on the plasma membrane correlate with angiogenic functions in vitro and in rodent models. The intracellular RTK pool also regulates plasma membrane receptor availability and signaling pathways. Organs have specialized angiogenic functions essential to their distinct roles, supporting the hypothesis that plasma membrane and intracellular RTK concentrations vary across endothelial cells (ECs) from different organs. MethodsUsing quantitative flow cytometry on human ECs derived from dermis, umbilical vein, kidney, liver, and brain, we measured and statistically analyzed the concentrations of selected RTKs within ECs and on their plasma membranes. ResultsVEGFR1 exhibited the lowest concentrations on the plasma membrane (300–900 VEGFR1/cell) among VEGFRs. HDMECs (dermis) showed the lowest VEGFR1 level among the examined EC types. Whole-cell VEGFR1 concentrations were 2500–7500 VEGFR1/cell, with 12–26% located on the plasma membrane. The proportion of VEGFR2 located on the plasma membrane was higher at > 30%, except in HGMECs (kidney) where it was 24%. Plasma membrane VEGFR2 was significantly lower in HDMECs and HGMECs compared with HBMECs (brain), whereas whole-cell VEGFR2 levels were consistently in the range of 14,100–22,500 molecules/cell. VEGFR3 was the least localized to the plasma membrane, from 2% in HGMECs to 14% in HDMECs at the highest level of 4400 VEGFR3/cell. Whole-cell VEGFR3 concentrations ranged from 32,400 in HDMECs to 62,000 VEGFR3/cell in HLiSMECs (liver), with no significant differences among EC types. NRP1 was most abundant on the plasma membrane of HUVECs (umbilical vein) at 39,700 NRP1/cell; other ECs displayed 26,000–29,900 NRP1/cell, approximately 5-fold higher than the numbers of VEGFRs. Across EC types, Axl was present on the plasma membrane at levels (6900–12,200 Axl/cell) similar to those of VEGFR2. ConclusionsWe quantified and statistically analyzed plasma membrane and whole-cell expression of angiogenic RTKs across cultured human ECs from five different organs. Our findings suggest that RTK protein distribution might not fully reflect the differential angiogenic capacities in cultured ECs. In vitro monoculture conditions might reduce EC organ-specific features essential for refining vascular models. 

Abstract Obesity is a global health crisis, with its prevalence particularly severe in the United States, where over 42% of adults are classified as obese. Obesity is driven by complex molecular and tissue-level mechanisms that remain poorly understood. Among these, angiogenesis—primarily mediated by vascular endothelial growth factor (VEGF-A)—is critical for adipose tissue expansion but presents unique challenges for therapeutic targeting due to its intricate regulation. Systems biology approaches have advanced our understanding of VEGF-A signaling in vascular diseases, but their application to obesity is limited by scattered and sometimes contradictory data. To address this gap, we performed a comprehensive analysis of the existing literature to synthesize key findings, standardize data, and provide a holistic perspective on the adipose vascular microenvironment. The data mining revealed five key findings: (1) obesity increases adipocyte size by 78%; (2) vessel density in adipose tissue decreases by 51% in obese mice, with vessels being 47–58% smaller and 4–9 times denser in comparison with tumor vessels; (3) capillary basement membrane thickness remains similar regardless of obesity; (4) VEGF-A shows the strongest binding affinity for VEGFR1, with four times stronger affinity for VEGFR2 than for NRP1; and (5) binding affinities measured by radioligand binding assay and surface plasmon resonance (SPR) are significantly different. These consolidated findings provide essential parameters for systems biology modeling, new insights into obesity-induced changes in adipose tissue, and a foundation for developing angiogenesis-targeting therapies for obesity. 

While traditional economics assumes that humans are fully rational agents who always maximize their expected utility, in practice, we constantly observe apparently irrational behavior. One explanation is that people have limited computational power, so that they are, quite rationally, making the best decisions they can, given their computational limitations. To test this hypothesis, we consider the multi-armed bandit (MAB) problem. We examine a simple strategy for playing an MAB that can be implemented easily by a probabilistic finite automaton (PFA). Roughly speaking, the PFA sets certain expectations, and plays an arm as long as it meets them. If the PFA has sufficiently many states, it performs near-optimally. Its performance degrades gracefully as the number of states decreases. Moreover, the PFA acts in a “human-like” way, exhibiting a number of standard human biases, like an optimism bias and a negativity bias.