Endothelial-Mesenchymal Transition in Cardiovascular Pathophysiology

Endothelial cells form the inner lining of blood vessels and maintain vascular homeostasis. Under certain stimuli, they undergo endothelial-mesenchymal transition (EndMT), a phenotypic conversion characterised by loss of endothelial markers and gain of mesenchymal traits. Initially recognised as a key process in embryonic heart development, EndMT has emerged as a driver of adult cardiovascular pathologies, including atherosclerosis, valvular disease, myocardial fibrosis and post-infarction remodelling. This transition is orchestrated by cytokines such as transforming growth factor beta (TGF-β), mechanical cues like shear stress and epigenetic modifiers including DNA methyltransferases. EndMT generates heterogeneous cell populations that contribute to extracellular matrix remodelling, inflammation and plaque instability, yet may also facilitate vascular repair. Recent advances in single-cell transcriptomics and lineage tracing have revealed that EndMT exists along a continuum of dynamic states, some of which are reversible. Targeting specific signalling axes or epigenomic regulators offers new avenues for therapeutic intervention. As cardiovascular disease remains a leading cause of global mortality, elucidating the mechanisms and timing of EndMT promises to refine strategies for limiting maladaptive remodelling while preserving regenerative functions.

Research from Nature Portfolio

Studies using endothelial lineage tracing and transcriptomic profiling have demonstrated that EndMT-derived cells are abundant in atherosclerotic plaques, co-expressing endothelial and fibroblast markers and contributing to collagen remodelling and plaque vulnerability. Single-cell RNA sequencing of post-myocardial infarction models has delineated a transient EndMT programme in which endothelial cells acquire mesenchymal genes alongside metabolic and inflammatory signatures before reverting to an endothelial state during repair. Foundational work on endothelial plasticity has uncovered transcriptional networks that balance arterial, venous and mesenchymal fates, identifying key regulators that preserve endothelial identity or drive pathological transition under stress.

Endothelial-Mesenchymal Transition in Cardiovascular Pathophysiology publication trend

The graph below shows the total number of articles in endothelial-mesenchymal transition in cardiovascular pathophysiology across all publications each year (not limited to Nature Index journals).

Technical terms

Endothelial-Mesenchymal Transition (EndMT): A cellular transdifferentiation programme in which endothelial cells lose characteristic markers and gain mesenchymal properties, contributing to vascular remodelling and fibrosis.

Transforming Growth Factor Beta (TGF-β): A family of cytokines central to development and a potent inducer of EndMT via SMAD-dependent signalling.

Shear stress: The tangential force exerted by circulating blood on the endothelial surface, influencing cell behaviour and gene expression.

Lineage tracing: An experimental method to label and track the fate of specific cell populations over time in vivo.

Single-cell RNA sequencing (scRNA-seq): A technique that profiles gene expression at the individual cell level, revealing heterogeneous transitional states during EndMT.

References

1. Endothelial to mesenchymal transition: at the axis of cardiovascular health and disease. Cardiovascular Research (2024).
2. DNMT1 mediates the disturbed flow-induced endothelial to mesenchymal transition through disrupting β-alanine and carnosine homeostasis. Theranostics (2023).
3. Endothelial to mesenchymal transition is common in atherosclerotic lesions and is associated with plaque instability. Nature Communications (2016).
4. The molecular basis of endothelial cell plasticity. Nature Communications (2017).
5. Single cell sequencing reveals endothelial plasticity with transient mesenchymal activation after myocardial infarction. Nature Communications (2021).