A conundrum of arterialized capillaries and vascular dilation in chronic limb-threatening ischaemia

Graphical Abstract Graphical Abstract The contrast of the microvascular niche between healthy skeletal muscle (left) and muscle obtained from a patient is quite apparent. In muscle of a patient with chronic limb-threatening ischaemia (CLTI), muscle fibres are no longer normal; macrophages are proinflammatory (shown as cytotoxic), endothelial cells (ECs) have gone from all normal (left) to many that have undergone endothelial–mesenchymal transition (Endo-MT); smooth muscle cells (SMCs) have transitioned from normal to synthetic; proteins [small blue dots of vascular endothelial growth factor (VEGF) protein, for example] are less retained in the vasculature due to the increased permeability. ECs express VEGF receptor 2 (VEGFR2), but any action of VEGF should not be viewed as specific to ECs as other cell types with the microvascular niche express VEGFR1. What is not apparent is whether the process across all the cells is reversible, as shown by the broken arrow going from right to left