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Endothelial Cells in Vascular Health and Immunity

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 20 August 2026 | Viewed by 883

Special Issue Editors


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Guest Editor
Department of Pediatrics, Northwestern University, Evanston, IL 60208, USA
Interests: adult stem cells; exosomes; angiogenesis; ischemic heart disease

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Guest Editor
Division of Critical Care, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Interests: lung injury; pneumonia; pulmonary pathology; vascular biology

Special Issue Information

Dear Colleagues,

Endothelial cells are central regulators of vascular homeostasis, immune responses, and tissue repair across multiple organ systems. Dysfunction of the endothelium contributes to the pathogenesis of cardiovascular, renal, and pulmonary diseases, including atherosclerosis, ischemia–reperfusion injury, acute kidney injury, chronic kidney disease, and acute lung injury. Beyond these, endothelial abnormalities are implicated in systemic inflammatory disorders, metabolic syndromes, and cancer. This Special Issue of International Journal of Molecular Sciences aims to highlight recent advances in understanding endothelial biology, mechanisms of endothelial dysfunction, and innovative therapeutic strategies targeting endothelial cells. Submissions that explore molecular pathways, immune interactions, regenerative approaches, and translational applications, with the goal of improving diagnosis, treatment, and outcomes across diverse disease contexts, are encouraged.

This Special Issue is supervised by Dr. Junjie Yang, assisted by Dr. Xianming Zhang (Research Associate Professor, Northwestern University).

Dr. Junjie Yang
Dr. Xianming Zhang
Guest Editors

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Keywords

  • endothelial cells
  • vascular health
  • cardiovascular disease
  • kidney disease
  • lung injury
  • inflammation
  • regenerative medicine
  • molecular therapy

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Published Papers (1 paper)

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Research

23 pages, 2059 KB  
Article
Functional Differences Between Typical and Multinucleated Endothelial Cells Under Low-Density Lipoprotein Exposure
by Vadim Cherednichenko, Diana Kiseleva, Ulyana Khovantseva, Denis Breshenkov, Rustam Ziganshin, Olga Dymova, Tatiana Kirichenko, Eduard Charchyan and Alexander M. Markin
Int. J. Mol. Sci. 2026, 27(5), 2425; https://doi.org/10.3390/ijms27052425 - 6 Mar 2026
Viewed by 511
Abstract
Endothelial cells are key regulators of vascular homeostasis, and their dysfunction plays a central role in the development of atherosclerosis and other cardiovascular diseases. Multinucleated variant endothelial cells (MVECs) have been described in pathological vascular regions; however, their functional properties remain poorly characterized. [...] Read more.
Endothelial cells are key regulators of vascular homeostasis, and their dysfunction plays a central role in the development of atherosclerosis and other cardiovascular diseases. Multinucleated variant endothelial cells (MVECs) have been described in pathological vascular regions; however, their functional properties remain poorly characterized. The aim of the present study was to compare lipid handling, inflammatory activation, barrier-associated features, and secretory profiles of typical endothelial cells (TECs, EA.hy926 line) and MVECs under low-density lipoprotein (LDL) exposure. MVECs were generated by polyethylene glycol-induced fusion of EA.hy926 cells and incubated with LDL under standardized conditions. Intracellular cholesterol accumulation was assessed biochemically, cytokine secretion was quantified by ELISA, gene expression of inflammatory, endothelial, junctional, and vasoactive markers was analyzed by quantitative real-time PCR, and the endothelial secretome was characterized using data-independent acquisition liquid chromatography–tandem mass spectrometry (DIA-LC-MS). MVECs demonstrated enhanced cholesterol accumulation compared with TECs following LDL exposure. At the transcriptional level, MVECs were characterized by elevated basal expression of proinflammatory markers, including IL1B, IL6, and NFKB1, and showed a markedly amplified IL6 and IL8 response to LDL. In parallel, MVECs exhibited reduced expression of genes associated with antioxidant defense (SOD1), barrier integrity (TJP1), and hemostatic function (VWF). Consistent with transcriptional data, mass spectrometry-based secretome analysis revealed decreased secretion of von Willebrand factor (vWF), vascular endothelial growth factor C (VEGFC), and endothelin-1 (EDN1) by MVECs, accompanied by increased secretion of tissue-type plasminogen activator (t-PA). Functional enrichment analysis of secretome-associated proteins highlighted pathways related to extracellular matrix–receptor interaction, focal adhesion, cell adhesion molecules, complement and coagulation cascades, and leukocyte transendothelial migration. In contrast, TECs demonstrated a more pronounced transcriptional response in EDN1, consistent with their role in vascular tone regulation. Immunocytochemical analysis further revealed altered subcellular distribution of the tight junction protein ZO-1 in MVECs, indicating junctional destabilization. Taken together, these results indicate that MVECs represent a distinct endothelial phenotype characterized by enhanced lipid accumulation, sustained proinflammatory activation, altered secretory signaling, and reduced barrier and hemostatic potential. Such features suggest that MVECs may contribute to the maintenance of chronic endothelial dysfunction and vascular inflammation under conditions of lipid overload. Full article
(This article belongs to the Special Issue Endothelial Cells in Vascular Health and Immunity)
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