Epidermal Growth Factor Receptor Signaling in Vascular Biology

The epidermal growth factor receptor (EGFR) is a membrane-bound tyrosine kinase that integrates signals from multiple ligands to regulate vascular cell behaviour. Upon ligand engagement, EGFR undergoes dimerisation and autophosphorylation, triggering downstream cascades such as the MAPK, PI3K/Akt and STAT pathways. In endothelial cells, EGFR controls barrier integrity, nitric oxide production and angiogenic responses, while in vascular smooth muscle cells it governs proliferation, migration and contractile function. Cross-talk with G-protein-coupled receptors, notably the angiotensin II type 1 receptor, occurs via ligand shedding, cytosolic kinases or direct heteromerisation, resulting in transactivation and amplified signalling. Dysregulated EGFR activity contributes to endothelial dysfunction, inflammation, oxidative stress, neointimal hyperplasia, hypertension and atherosclerotic plaque progression. Although EGFR inhibitors are established in oncology, their repurposing for vascular disease holds promise for stabilising plaques, restoring compliance and reducing vascular remodelling. Tailoring EGFR modulation to specific vessel beds and cell types may offer targeted therapies that preserve physiological repair while preventing pathological remodelling.

Research from Nature Portfolio

Recent studies have revealed vessel type and sex-specific responses to EGFR activation in female arterial endothelial cells. Activation elicits pro- or anti-inflammatory programmes in coronary versus aortic cells, with consequences for leukocyte adhesion and cytokine expression. This work emphasises endothelial heterogeneity and the need to tailor interventions for vascular inflammation. Foundational work has also demonstrated that pharmacological inhibition of EGFR signalling attenuates diet-induced atherosclerotic plaque formation by reducing macrophage infiltration, oxidative stress and smooth muscle proliferation, suggesting EGFR as a viable target to stabilise vulnerable lesions and restore vessel wall homeostasis.

Epidermal Growth Factor Receptor Signaling in Vascular Biology publication trend

The graph below shows the total number of articles in epidermal growth factor receptor signaling in vascular biology across all publications each year (not limited to Nature Index journals).

Technical terms

Epidermal growth factor receptor (EGFR): A membrane-bound receptor tyrosine kinase that mediates cellular responses to EGF-like ligands.

Transactivation: Indirect activation of EGFR by alternate receptors or proteases without direct ligand binding.

Endothelial cells: Cells lining the interior surface of blood vessels, critical for barrier function and vascular homeostasis.

Vascular smooth muscle cells (VSMCs): Muscle cells in the vessel wall responsible for tone, contractility and structural integrity.

Mitogen-activated protein kinase (MAPK): A downstream signalling cascade that regulates proliferation, differentiation and inflammation.

Heteromerisation: Formation of a complex between different receptor types, modulating signalling specificity and strength.

References

1. Direct GPCR-EGFR interaction enables synergistic membrane-to-nucleus information transfer. Cellular and Molecular Life Sciences (2024).
2. The role of EGFR in vascular AT1R signaling: From cellular mechanisms to systemic relevance. Biochemical Pharmacology (2023).
3. EGFR activation differentially affects the inflammatory profiles of female human aortic and coronary artery endothelial cells. Scientific Reports (2023).
4. Assessment of the Role of Endothelial and Vascular Smooth Muscle EGFR for Acute Blood Pressure Effects of Angiotensin II and Adrenergic Stimulation in Obese Mice. Biomedicines (2023).
5. Inhibition of epidermal growth factor receptor attenuates atherosclerosis via decreasing inflammation and oxidative stress. Scientific Reports (2017).
6. The Epidermal Growth Factor Receptor and Its Ligands in Cardiovascular Disease. International Journal of Molecular Sciences (2013).