ReviewPathophysiology : the official journal of the International Society for Pathophysiology2026
Time-Varying Low-Frequency Electromagnetic Fields and Endothelial Angiogenesis: From Early In Vitro Discoveries to Emerging Mechanisms.
Review in Pathophysiology : the official journal of the International Society for Pathophysiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND/
objectivesTime-varying low-frequency electromagnetic fields (LF-EMFs), including pulsed electromagnetic fields (PEMFs) and sinusoidal low-frequency electromagnetic fields, have been investigated as modulators of tissue repair and vascular remodeling. Although numerous studies report pro-angiogenic effects in endothelial systems, the underlying mechanisms remain incompletely understood. This review synthesizes evidence for LF-EMF-induced endothelial angiogenesis and evaluates emerging mechanistic explanations.
methodsLiterature was identified through searches of PubMed, Web of Science, and Google Scholar through March 2026. Peer-reviewed studies emphasizing in vitro endothelial angiogenesis models were prioritized, with selected in vivo studies included when relevant to mechanistic interpretation. The review was conducted as a narrative synthesis rather than a systematic review or meta-analysis.
resultsExperimental evidence indicates that LF-EMF exposure can enhance endothelial proliferation, migration, sprouting, tube formation, and survival across diverse model systems. Reported mechanisms include modulation of growth factor signaling, calcium-dependent pathways, nitric oxide production, cytoskeletal remodeling, and mechanotransduction. Reexamination of early ultrastructural studies suggests that membrane ruffling, vacuole formation, and vesicular structures observed following LF-EMF exposure may be interpreted within the framework of macropinocytosis and vesicular trafficking, providing a potential mechanistic link between electromagnetic stimulation and endothelial morphogenesis.
conclusionsCurrent evidence supports the conclusion that LF-EMFs can modulate key endothelial processes involved in angiogenesis and vascular remodeling. Membrane trafficking and macropinocytosis provide a biologically plausible framework linking historical observations with contemporary endothelial cell biology, although direct experimental validation is needed. Future progress will require standardized exposure paradigms and mechanistic studies using physiologically relevant angiogenesis models.
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