Endothelial Function and Cardiovascular Health

The vascular endothelium is a dynamic monolayer of cells lining the inner surface of blood vessels, serving as a critical interface between circulating blood and the vessel wall. By releasing vasodilators, notably nitric oxide, and vasoconstrictors, it modulates vascular tone, fluid filtration, coagulation, and immune cell trafficking. Endothelial cells sense and respond to haemodynamic forces through mechanotransduction pathways that translate shear stress into biochemical signals. Disruption of endothelial homeostasis—termed endothelial dysfunction—is implicated in the initiation and progression of atherosclerosis, hypertension, heart failure and other cardiovascular disorders. Emerging data reveal that endothelial heterogeneity and metabolic adaptation underpin both physiological repair and pathological remodelling. Understanding the molecular mechanisms that govern endothelial cell phenotype offers routes to novel diagnostics and targeted therapies aimed at preserving vascular health and reducing global cardiovascular burden.

Research from Nature Portfolio

Recent studies have illuminated how disturbed flow patterns reprogramme endothelial cells towards pro-atherogenic states. Single-cell transcriptomic and chromatin accessibility analyses in animal models demonstrate that oscillatory shear stress triggers inflammatory gene programmes, endothelial-to-mesenchymal and endothelial-to-immune-like transitions, and metabolic shifts. These findings identify mechanosensors and downstream pathways as potential therapeutic targets to forestall lesion development. Complementary work has shown that increased glycolytic flux driven by AMPKα1 under disturbed flow preserves endothelial viability and barrier integrity. Loss of AMPKα1 in the endothelium diminishes glucose uptake, compromises barrier function and accelerates plaque formation, whereas restoration of glycolysis confers vascular protection. Together, these investigations reveal metabolic reprogramming as a protective adaptation in regions susceptible to atherogenesis.

Endothelial Function and Cardiovascular Health publication trend

The graph below shows the total number of articles in endothelial function and cardiovascular health across all publications each year (not limited to Nature Index journals).

Technical terms

Endothelial dysfunction: A pathological state in which the endothelium loses its physiological balance of vasodilation, anti-thrombotic and anti-inflammatory functions.

Shear stress: The tangential force exerted by blood flow on the endothelial surface, which influences cell alignment, gene expression and vascular tone.

Mechanotransduction: The process by which cells convert mechanical stimuli, such as shear stress, into biochemical signals that regulate cellular behaviour.

Nitric oxide bioavailability: The extent to which nitric oxide is produced and remains active within the vascular wall, critical for vasodilation and inhibition of platelet aggregation.

Atherosclerosis: A chronic inflammatory disease characterised by lipid accumulation, endothelial activation and plaque formation within arterial walls.

Endothelial-to-mesenchymal transition: A phenotypic switch in which endothelial cells acquire mesenchymal characteristics, contributing to vascular remodelling and fibrosis.

References

1. Flow-induced reprogramming of endothelial cells in atherosclerosis. Nature Reviews Cardiology (2023).
2. Revealing the Role of Zinc Ions in Atherosclerosis Therapy via an Engineered Three‐Dimensional Pathological Model. Advanced Science (2023).
3. Endothelial dysfunction: molecular mechanisms and clinical implications. MedComm (2024).
4. PRKAA1/AMPKα1-driven glycolysis in endothelial cells exposed to disturbed flow protects against atherosclerosis. Nature Communications (2018).
5. Endothelial Dysfunction in Hypertension: Current Concepts and Clinical Implications. Frontiers in Medicine (2022).