Extracellular Vesicles in Atherosclerosis: Decoding Communication and Repair

Code: BC-DTP_2026_32

Title: Extracellular Vesicles in Atherosclerosis: Decoding Communication and Repair

Primary Supervisor: Manikandan Subramanian

Email: m.subramanian@qmul.ac.uk

Institute: William Harvey Research Institute

Secondary Supervisor: Mauro Perretti

Email: m.perretti@qmul.ac.uk

Institute: William Harvey Research Institute

Lay Summary:

Atherosclerosis is a disease where fatty deposits build up inside blood vessels, gradually narrowing them and restricting blood flow to the heart and brain. This can lead to heart attacks and strokes which are major causes of death and illness worldwide. Although cholesterol-lowering medications like statins help, many patients still suffer heart attacks and strokes, highlighting the urgent need for new treatment approaches.

Atherosclerosis is characterised by the accumulation of blood-borne and resident cells, lipids, fibrotic tissue and more into what is called ‘a plaque’. The main problem is when these plaques become unstable. In these "vulnerable plaques," dead cells accumulate in the center while the protective outer layer becomes thinner and weaker, making the plaque more likely to rupture and cause a blood clot.

Our recent research showed that when immune cells called macrophages clean up dead cells (a process called efferocytosis), they release tiny packages of molecules called extracellular vesicles (EVs). These vesicles act as messengers between cells, promoting healing and reducing inflammation. In mice, these vesicles successfully stabilised plaques by reducing dead cell buildup and thickening the protective outer layer.

Interestingly, this treatment also changed smooth muscle cells which are important structural cells in blood vessels by increasing their numbers and boosting collagen production. This remodelling strengthened and stabilised the plaques.

This research project aims to understand exactly how these vesicles reprogram smooth muscle cells and change their behaviour. By combining laboratory experiments with animal models, we hope to develop new therapies that stabilise plaques and prevent heart attacks and stroke.

Aims:

Aim 1: Characterisation of Effero EV-induced phenotypic and functional changes in vascular SMCs.

Aim 2: Mechanistic basis of Effero EV-induced phenotypic and functional changes in vascular SMCs.

Aim 3: Functional validation of mechansisms in a preclinical model of murine atherosclerosis. 

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