Impaired lipid homeostasis and mitochondrial dysfunction in critical limb ischaemia caused by arteriosclerosis obliterans.

Abstract

Critical limb ischaemia (CLI), a severe peripheral artery disease, reduces blood flow, disrupting lipid metabolism and mitochondrial function. This leads to muscle loss, impaired repair, and greater limb loss risk. Standard diagnostics emphasise imaging and perfusion, often missing metabolic changes. The LIPID-CLI framework uses high-resolution mass spectrometry to analyse lipid shifts under mitochondrial stress. Biopsy limits shifted focus to blood markers reflecting tissue lipids. Altered ceramides and phospholipids indicate lipid-mitochondrial dysfunction and may serve as non-invasive biomarkers for early CLI detection and treatment. The method improves ceramides (400 mL), phospholipid ratio (1.5), acylcarnitines (6 L), OxPLs (300 mL), index score (<0.4), and mediator levels (200 mL). The reduction denotes decreased ceramide concentration (µmol/mL or ng/mL), normalised to total lipid content in affected tissues. This measure reflects how ceramide alterations disrupt lipid homeostasis and mitochondrial function in critical limb ischaemia (CLI).