Apoptosis and efferocytosis as mechanisms of impaired fibrotic tissue repair in diabetes associated vascular complications

Individuals with type 2 diabetes (T2D) die prematurely due to cardiovascular complications caused by an aggravated arterial atherosclerotic plaque formation.

We provided evidence for an impaired arterial tissue repair, linked to cell death (apoptosis) and removal of dead cells (efferocytosis), to be a potential cause.Here I aim, for the first time, to characterise T2D arterial tissue repair and to explore if this process is affected by apoptosis/efferocytosis to identify new therapeutic targets.I use human atherosclerotic plaques, blood, imaging and follow up from three of the most well characterised cardiovascular biobanks in the world (established).

Tissue repair, apoptosis/efferocytosis will be characterised by a novel mass spectrometry, imaging and ELISA (ongoing, done in 3-6-years). Using a unique cell/tissue sequencing approach (single-/spatial-/bulk-RNAseq) and mass cytometry (collab.

Oxford University) I will create the first human plaque/blood cell phenotype/function atlas to identify key genes/cells (ongoing, validation done in 5-years) in atherosclerosis and T2D.

Circulating markers will be studied using follow up and repeated arterial ultrasounds (ongoing-done in 1-3-years, MDC and SUMMIT collab.).My project has a close clinical link and the cell atlas will be a great asset for the whole field to reveal therapeutic targets.

New therapies and biomarkers, targeting T2D, would be of enormous value to reduce individual suffering and of great socioeconomic importance.