Research from Queen Mary University of London, published today in the journal Science Signaling, provides new insights into the prevention of cardiovascular disease by shedding light on the previously unknown role of the protein Neuropilin-1.
Immunostaining visualising the endothelium of a mouse aorta.
The inner surface of the blood vessels is covered by a layer of cells that regulates oxygen and nutrient delivery to organs and tissues. This layer, known as the endothelium, is essential for keeping the blood vessels healthy. Age, lack of physical exercise, smoking and a diet rich in fat induce degeneration of these cells promoting high blood pressure and blood vessel blockage. Blockage of vessels supplying the heart or the brain causes heart attack and stroke, resulting in the death of the tissues due to oxygen and nutrient shortage.
In the study, researchers found that a protein called Neuropilin-1 helps the cells lining the inner surface of blood vessels to remain healthy and prevents atherosclerosis, the build-up of fatty material inside the arteries leading to blood vessel blockage. The study describes for the first time the role of this protein in maintaining a healthy endothelium and provides evidence that Neuropilin-1 could be a therapeutic target in vascular disease.
Neturopilin-1 has been mainly studied as a protein that in endothelial cells promotes the formation of new vessels (a process called angiogenesis) from pre-existing ones during embryonic development. It has also been shown to promote angiogenesis in pathological conditions such as tumour growth and eye diseases such as diabetic retinopathy and age-related macular degeneration. No previous studies have investigated whether Neuropilin-1 has a role in the pathophysiology of cardiovascular disease. This study shows that Neuropilin-1 has a key role in protecting blood vessels from pathological changes typical of cardiovascular diseases.
Dr Claudio Raimondi, Lecturer in Endothelial Cell Biology at Queen Mary University of London and lead author, said: “This study advances our understanding of the mechanism that protects the endothelium lining the inner surface of the blood vessels and identifies Neuropilin-1 as a major orchestrator of cellular signals that protects from the development of atherosclerosis and vascular inflammation.
“Atherosclerosis is a major underlying pathology in cardiovascular disease, triggered by the interplay between endothelial cell dysfunction, vascular lipid retention and inflammation leading to a blockage of the blood vessel. Dysfunction of the endothelium of the arterial vasculature is an early important contributor to the pathobiology of atherosclerotic and hypertension. Our findings provide the basis to develop potential therapeutic tools aimed at promoting specific signals modulated by Neuropilin-1. “Therapeutic tools that selectively promote the Neuropilin-1 pathways identified in this study have the potential to improve the outcome of patients affected by myocardial infarction, stroke and neurodegenerative diseases, where endothelial damage and dysfunction are common, underlying characteristics. Furthermore, our study shows that Neuropilin-1 expression is modulated by signals that protect the endothelium and therefore our findings open to the possibility that Neuropilin-1 could be a potential biomarker of vascular health, with its expression reduced in the endothelium of patients with cardiovascular disease.”
This study was funded by the British Heart Foundation and is a collaboration between researchers at Queen Mary University of London, Imperial College, and St. George’s University.
Research paper: Bosseboeuf E, Raimondi C et al. Neuropilin-1 interacts with VE-cadherin and TGFBR2 to stabilize adherens junctions and prevent activation of endothelium under flow. Sci. Signal.16,eabo4863 (2023). DOI: 10.1126/scisignal.abo4863