Abstract Th0082: Multi-omics Approach of Peripheral Artery Disease Patient Gastrocnemius Describes Disease Progression

Peripheral artery disease (PAD) is an atherosclerotic disease that causes ischemic myopathy in the affected skeletal muscle. Understanding the development of myopathy and its progression from early-stage PAD to late-stage PAD is critical for advancing the understanding of the disease biology and improving patient care. In this study, gastrocnemius samples were collected from 21 non-PAD patients, 45 intermittent claudication (IC) patients, and 30 critical limb ischemia (CLI) patients for whole transcriptomics and spatial transcriptomics. Transcriptomics showed a unique transcript expression profile for both IC and CLI. Emerging biological processes included proton motive force-driven mitochondrial ATP synthesis, mitochondrial respiratory chain complex 1 assembly, proton transmembrane transport, muscle contraction, generation of precursor metabolites and energy, and response to hypoxia. After spatial transcriptomic analysis, it was observed that gene expression changes in IC patients are localized within the vessels, whereas there are myofiber gene expression changes in CLI patients. It was also observed that morphologically damaged myofibers have a unique gene expression profile compared to morphologically healthy ones in the same tissue, indicating myofiber heterogeneity within CLI patients. Gene expression is altered in PAD-induced myopathy, beginning in IC patients and progressing significantly in CLI patients. This alteration is spatially regulated and affects several critical physiological processes.