New potential target for treating vascular disease identified

Vascular smooth muscle cell (VSMC) activation plays a crucial role in the development of multiple vascular diseases. In a novel study in The American Journal of Pathology, published by Elsevier, researchers found that when fragile-X related protein-1 (FXR1) is absent, VSMC proliferate more slowly, become senescent, and scar tissue (neointima) development is reduced. Therefore, drugs targeting FXR1 may treat vascular proliferative diseases.

To extend their understanding of the impact of the absence of FXR1, investigators performed RNA-sequencing on FXR1-depleted human VSMCs. Their results suggest that FXR1 appears to stabilize a group of transcripts involved in control of the cell cycle, most of which are associated with proliferation and cell division. In addition, they noted an increase in beta galactosidase and gamma H2AX, molecules indicative of cell senescence.

Next, to understand how the absence of FXR1 would affect vascular occlusive disease, they developed a mouse model to specifically deplete FXR1 in the smooth muscles upon drug induction. The mice were subjected to carotid ligation, which is a model of vascular stenosis. Drug-induced depletion of FXR1 in smooth muscle cells protected the mice against neointima formation following injury. Injured arteries had a gene expression profile similar to human VSMC following FXR1 knockdown.

Reference:

Genetic Deletion of FXR1 Reduces Intimal Hyperplasia and Induces Senescence in Vascular Smooth Muscle Cells, American Journal Of Pathology, DOI 10.1016/j.ajpath.2023.01.006