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Endothelial cells (ECs) mediate several biological functions that are relevant to atherosclerosis and coronary artery disease (CAD), regulating an array of vital processes including vascular tone, wound healing, reactive oxygen species, shear stress response, and inflammation. Although which of these functions is linked causally with CAD development and/or progression is not yet known, genome-wide association studies have implicated more than 400 loci associated with CAD risk, among which several have shown EC-relevant functions. Given the arduous process of mechanistically interrogating single loci to CAD, high-throughput variant characterization methods, including pooled Clustered Regularly Interspaced Short Palindromic Repeats screens, offer exciting potential to rapidly accelerate the discovery of bona fide EC-relevant genetic loci. These discoveries in turn will broaden the therapeutic avenues for CAD beyond lipid lowering and behavioral risk modification to include EC-centric modalities of risk prevention and treatment.
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http://dx.doi.org/10.1016/j.ajpath.2023.09.012 | DOI Listing |
Oncogene
September 2025
Division of Neurosurgery, Children's Hospital Los Angeles, Los Angeles, CA, USA.
It has become evident from decades of clinical trials that multimodal therapeutic approaches with focus on cell intrinsic and microenvironmental cues are needed to improve understanding and treat the rare, inoperable, and ultimately fatal diffuse intrinsic pontine glioma (DIPG), now categorized as a diffuse midline glioma. In this study we report the development and characterization of an in vitro system utilizing 3D Tumor Tissue Analogs (TTA), designed to replicate the intricate DIPG microenvironment. The innate ability of fluorescently labeled human brain endothelial cells, microglia, and patient-derived DIPG cell lines to self-assemble has been exploited to generate multicellular 3D TTAs that mimic tissue-like microstructures, enabling an in- depth exploration of the spatio-temporal dynamics between neoplastic and stromal cells.
View Article and Find Full Text PDFJ Orthop Sci
September 2025
Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, North 15 West 7, Kita-Ku, Sapporo, Hokkaido 060-8638, Japan. Electronic address:
Background: Angiosarcoma is a rare and aggressive malignancy arising from vascular endothelial cells, with distinct subtypes originating in bone (AS-B) and soft tissue (AS-ST). While these subtypes share pathological similarities, differences in clinical outcomes remain unclear due to limited data. This study aimed to compare the clinical features, treatment strategies, and survival outcomes between AS-B and AS-ST using the Surveillance, Epidemiology, and End Results (SEER) database.
View Article and Find Full Text PDFNitric Oxide
September 2025
Department of Physics, Wake Forest University, Winston-Salem, NC 27109, USA; Translational Science Center, Wake Forest University, Winston-Salem, NC 27109, USA. Electronic address:
We recently demonstrated a rapid reaction between labile ferric heme and nitric oxide (NO) in the presence of reduced glutathione (GSH) or other small thiols in a process called thiol-catalyzed reductive nitrosylation, yielding a novel signaling molecule, labile nitrosyl ferrous heme (NO-ferroheme), which we and others have shown can regulate vasodilation and platelet homeostasis. Red blood cells (RBCs) contain high concentrations of GSH, and NO can be generated in the RBC via nitrite reduction and/or RBC endothelial nitric oxide synthase (eNOS) so that NO-ferroheme could, in principle, be formed in the RBC. NO-ferroheme may also form in other cells and compartments, including in plasma, where another small and reactive thiol species, hydrogen sulfide (HS/HS), is also present and may catalyze NO-ferroheme formation akin to GSH.
View Article and Find Full Text PDFJ Neurosci Methods
September 2025
Bioengineering College of Chongqing University, Chongqing University Central Hospital (Chongqing Emergency Medical Center), Chongqing, China; Chongqing Key Laboratory of Emergency Medicine, Chongqing, China. Electronic address:
Background: Current neurovascular unit isolation requires processing brain microvascular endothelial cells (BMECs) and neurons from separate animals, preventing concurrent analysis of neurovascular crosstalk within identical genetic/physiological contexts.
New Methods: We developed an enzymatic digestion/bovine serum albumin density gradient technique that enables the simultaneous isolation of neural tissue and microvascular segments from individual mice. The neural tissue was filtered and centrifuged for primary cortical neuron culture on poly-L-lysine-coated plates.
J Adv Res
September 2025
Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha P.O. Box 24144, Qatar. Electronic address:
Background: Studies on the interaction of cancer cells with other cells (fibroblasts, endothelial cells, and immune cells) of the tumor microenvironment (TME) have led to the development of many novel targeted therapies. More recently, the notion that neuronal cells of the TME could impact various processes supporting cancer progression has gained momentum. Tumor-associated neurons release neurotransmitters into the TME that, in turn, bind to specific receptors on different target cells, supporting cancer progression.
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