Atherosclerosis research - plaque monitoring and cell biology

Two new papers utilizing DRAQ5 to facilitate high quality cell sorting to downstream single cell RNA sequencing to unpick the molecular backdrop to atherosclerotic plaque cell biology.

In the first of these, from Muredach Reilly's lab at Columbia University, fibroblasts were profiled. Four distinct subpopulations were identified - all of which diminished in number upon onset of experimental atherosclerosis in mice.  Significantly, a CD26+ subpopulation migrated from the "adventitial" or external connective tissue layer in healthy individuals and into the innermost layer ("intima") upon atherosclerosis. Notably, these were found to localize to the fibrous cap of the lesion as determined by a combination of flow cytometry and immunohistochemistry. 

The suggestion is that this subpopulation may stabilize the plaque. It may be early to hypothesize if this is driven by other factors (e.g. unrelated inflammation) or whether it has implications for therapy since CD26 is normally expressed on vascular endothelial cells and is involved in cell adhesion.

In the second article, led by Jacob Bentzon with research teams in Madrid and Aarhus, the use of FDG-PET to monitor plaque progression was explored.  Using the data from transcriptomics, it was seen in a large animal model, pig, that glycolytic enzyme expression was reduced concomitant to FDG-PET signals and plaque regression in all associated cell types. 

This direct correlation to the observed FDG-PET signals indicated that PDG-PET imaging could be valuable in monitoring of atherosclerotic plaques as an aid to clinical management.

References:

Bashore AC, Coronel J, Xue C, Zhu LY, Reilly MP. Single-Cell Multimodal Profiling Reveals a Novel CD26+ Fibroblast Subpopulation in Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 2025 Jan 28. DOI:10.1161/ATVBAHA.124.322370

Nogales P, Velasco C, González-Cintado L, Sharysh D, Mota-Cobián A, Izquierdo-Serrano R, Torroja C, del Rio-Aledo D, Morales-Cano D, Mota RA, Benguría A. Atherosclerotic disease activity is associated with glycolytic enzyme expression across multiple cell types and is trackable by FDG-PET. Science translational medicine. 2025 Aug 13;17(811):eado6467.