Academic Journal
A biphasic effect of alcohol on endothelial plasticity through regulation of endothelial-to-mesenchymal transition.
| Τίτλος: | A biphasic effect of alcohol on endothelial plasticity through regulation of endothelial-to-mesenchymal transition. |
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| Συγγραφείς: | Liu W; Department of Surgery, University of Rochester Medical Center, Rochester, New York, United States., Gusti Y; Department of Surgery, University of Rochester Medical Center, Rochester, New York, United States., Athar F; Department of Surgery, University of Rochester Medical Center, Rochester, New York, United States., Rajendran NK; Department of Surgery, University of Rochester Medical Center, Rochester, New York, United States., Cahill PA; Vascular Biology and Therapeutics Laboratory, School of Biotechnology, Dublin City University, Dublin, Ireland., Redmond EM; Department of Surgery, University of Rochester Medical Center, Rochester, New York, United States. |
| Πηγή: | American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2026 Oct 01; Vol. 331 (4), pp. H1363-H1376. Date of Electronic Publication: 2026 Sep 15. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901228 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1539 (Electronic) Linking ISSN: 03636135 NLM ISO Abbreviation: Am J Physiol Heart Circ Physiol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Bethesda, Md. : American Physiological Society |
| Ιατρικοί όροι (MeSH): | Endothelial-Mesenchymal Transition*/drug effects , Ethanol*/pharmacology , Ethanol*/toxicity , Endothelial Cells*/drug effects , Endothelial Cells*/metabolism , Endothelial Cells*/pathology , Cell Plasticity*/drug effects , Carotid Artery Injuries*/pathology , Carotid Artery Injuries*/metabolism, Signal Transduction/drug effects ; Human Umbilical Vein Endothelial Cells/drug effects ; Human Umbilical Vein Endothelial Cells/metabolism ; Human Umbilical Vein Endothelial Cells/pathology ; Cell Movement/drug effects ; Cadherins/metabolism ; Coronary Vessels/drug effects ; Coronary Vessels/metabolism ; Coronary Vessels/pathology ; Cytokines/pharmacology ; Carotid Arteries/pathology ; Carotid Arteries/drug effects ; Carotid Arteries/metabolism ; Animals ; Humans ; Male ; Cells, Cultured ; Mice, Inbred C57BL ; Neointima ; Dose-Response Relationship, Drug ; Disease Models, Animal ; Cell Hypoxia ; Mice |
| Περίληψη: | Alcohol influences cardiovascular disease, but whether it does so by affecting endothelial plasticity is unknown. We tested whether alcohol regulates endothelial-to-mesenchymal transition (EndMT) to influence arterial pathology. Human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC) were exposed to inflammatory cytokines or hypoxia in the absence or presence of ethanol (5-100 mM). In vivo, carotid ligation was performed in mice gavaged with/without either daily moderate ethanol (2 drinks equivalent/day) or episodic binge exposure (7 drinks equivalent, 2 days/wk) and myoendothelial cells assessed. Cytokines and hypoxia induced EndMT in vitro characterized by loss of endothelial markers, increased mesenchymal markers, and enhanced migratory capacity. Low-to-moderate-dose ethanol (5-25 mM) attenuated marker changes, preserving endothelial phenotype, whereas high-dose ethanol (50-100 mM) either had no effect or exacerbated EndMT. The inhibitory effect of moderate-dose ethanol on cytokine- and hypoxia-induced changes in α-smooth muscle actin (αSMA) and cadherin-5 (Cdh5) expression was abrogated by γ-secretase inhibition, consistent with involvement of Notch signaling. Carotid ligation induced neointimal formation and accumulation of myoendothelial cells indicative of EndMT. Daily moderate-dose ethanol significantly attenuated neointimal hyperplasia and diminished the myoendothelial cell population, whereas in contrast, episodic binge ethanol exposure increased pathologic remodeling and myoendothelial cell abundance. Alcohol modulates endothelial transdifferentiation in a biphasic manner. Low-to-moderate-dose alcohol exposure suppresses EndMT and limits pathological remodeling, whereas higher level binge exposure promotes these processes. These findings identify regulation of endothelial plasticity as a potential novel mechanism linking alcohol consumption patterns to vascular disease risk.NEW & NOTEWORTHY We identify a previously unrecognized biphasic effect of alcohol on endothelial phenotypic plasticity. Low-to-moderate-dose alcohol suppresses endothelial-to-mesenchymal transition (EndMT), whereas high-level (binge) exposure promotes this proatherogenic process. Given the central role of EndMT in vascular remodeling and atherosclerosis, these findings provide a mechanistic framework linking alcohol consumption and cardiovascular disease risk - potentially explaining both the protective effect at low-to-moderate levels, and the detrimental impact of heavy alcohol use. |
| Σχόλια: | Update of: bioRxiv. 2026 Apr 16:2026.04.14.718463. doi: 10.64898/2026.04.14.718463.. (PMID: 42039518) |
| Grant Information: | RO1AA024082 HHS | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA); RO1AA031225 HHS | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) |
| Contributed Indexing: | Keywords: alcohol; atherosclerosis; cardiovascular disease; endothelial differentiation; endothelial-to-mesenchymal transition (EndMT) |
| Substance Nomenclature: | 3K9958V90M (Ethanol) 0 (Cadherins) 0 (Cytokines) |
| Entry Date(s): | Date Created: 20260915 Date Completed: 20260930 Latest Revision: 20260930 |
| Update Code: | 20261001 |
| DOI: | 10.1152/ajpheart.00310.2026 |
| PMID: | 42743242 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1522-1539 |
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| DOI: | 10.1152/ajpheart.00310.2026 |