Toll-Like Receptors in Ischaemia and Its Potential Role in the Pathophysiology of Muscle Damage in Critical Limb Ischaemia

Figure 3

Proposed pathophysiological mechanism of skeletal muscle damage in CLI. Skeletal muscle ischaemia initiates muscle cell apoptosis and necrosis leading to the release of endogenous ligands such as HMGB-1. Subsequently TLRs are activated in other viable muscle cells causing signalling through one or more TLR signalling pathways. This may lead to the activation of transcription factors such as NF-κB, AP-1, IRF 3, and 2. The consequent activation of transcription factors leads to the induction and release of proinflammatory cytokines, chemokines, and interferons that propagate the skeletal muscle damage.