Abstract
Peripheral artery disease (PAD) is a common atherosclerotic disease characterized by narrowed or blocked arteries in the lower extremities. Circulating serum biomarkers can provide significant insight regarding the disease progression. Here, we explore the metabolomics signatures associated with different stages of PAD and investigate potential mechanisms of the disease. We compared the serum metabolites of a cohort of 26 PAD patients presenting with claudication and 26 PAD patients presenting with critical limb ischemia (CLI) to those of 26 non-PAD controls. A difference between the metabolite profiles of PAD patients from non-PAD controls was observed for several amino acids, acylcarnitines, ceramides, and cholesteryl esters. Furthermore, our data demonstrate that patients with CLI possess an altered metabolomic signature different from that of both claudicants and non-PAD controls. These findings provide new insight into the pathophysiology of PAD and may help develop future diagnostic procedures and therapies for PAD patients.
Highlights
Peripheral artery disease (PAD) is an atherosclerotic condition of the arteries supplying the lower extremities
intermittent claudication (IC) patients were younger than critical limb ischemia (CLI) patients (p = 0.044) and CLI patients had a higher ratio of diabetes mellitus (p = 0.005)
We identified several metabolites that are altered in symptomatic PAD patients compared to non-PAD controls while identifying a distinct metabolomic signature associated with only CLI [15]
Summary
Peripheral artery disease (PAD) is an atherosclerotic condition of the arteries supplying the lower extremities. Work from several groups, including our own, has demonstrated significant degenerative changes in all the tissues of the chronically ischemic legs of patients with PAD, including skin, muscles, nerves, and subcutaneous tissues [5,6] These changes have been best studied in the skeletal muscle of the affected limbs [7,8,9] and demonstrate an acquired myopathy with significant metabolic components. The biochemical characteristics of this myopathy include mitochondrial dysfunction, accumulation of metabolic intermediates, increased oxidative damage, and cytokine upregulation [1,5,6,10,11,12,13,14] These metabolic myopathic changes are present in the legs of both IC and CLI patients, with the myopathy of CLI being more severe than that of IC [15]. PAD is directly associated with conditions like dyslipidemia, obesity or cachexia, diabetes, and insulin resistance, all of which involve dysregulation of metabolism and energy homeostasis [16,17]
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