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Article

Serum Metabolic Signatures of Chronic Limb-Threatening Ischemia in Patients with Peripheral Artery Disease

1
Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4M1, Canada
2
Department of Pharmacognosy, Alexandria University, Alexandria 21521, Egypt
3
Department of Surgery, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada
4
Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(6), 1877; https://doi.org/10.3390/jcm9061877
Received: 8 May 2020 / Revised: 30 May 2020 / Accepted: 10 June 2020 / Published: 16 June 2020
(This article belongs to the Special Issue Peripheral Artery Disease: From Diagnosis to Treatment)
Peripheral artery disease (PAD) is characterized by the atherosclerotic narrowing of lower limb vessels, leading to ischemic muscle pain in older persons. Some patients experience progression to advanced chronic limb-threatening ischemia (CLTI) with poor long-term survivorship. Herein, we performed serum metabolomics to reveal the mechanisms of PAD pathophysiology that may improve its diagnosis and prognosis to CLTI complementary to the ankle–brachial index (ABI) and clinical presentations. Non-targeted metabolite profiling of serum was performed by multisegment injection–capillary electrophoresis–mass spectrometry (MSI–CE–MS) from age and sex-matched, non-diabetic, PAD participants who were recruited and clinically stratified based on the Rutherford classification into CLTI (n = 18) and intermittent claudication (IC, n = 20). Compared to the non-PAD controls (n = 20), PAD patients had lower serum concentrations of creatine, histidine, lysine, oxoproline, monomethylarginine, as well as higher circulating phenylacetylglutamine (p < 0.05). Importantly, CLTI cases exhibited higher serum concentrations of carnitine, creatinine, cystine and trimethylamine-N-oxide along with lower circulating fatty acids relative to well matched IC patients. Most serum metabolites associated with PAD progression were also correlated with ABI (r = ±0.24−0.59, p < 0.05), whereas the ratio of stearic acid to carnitine, and arginine to propionylcarnitine differentiated CLTI from IC with good accuracy (AUC = 0.87, p = 4.0 × 10−5). This work provides new biochemical insights into PAD progression for the early detection and surveillance of high-risk patients who may require peripheral vascular intervention to prevent amputation and premature death. View Full-Text
Keywords: peripheral artery disease; serum; metabolomics; intermittent claudication; chronic limb-threatening ischemia peripheral artery disease; serum; metabolomics; intermittent claudication; chronic limb-threatening ischemia
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MDPI and ACS Style

Azab, S.M.; Zamzam, A.; Syed, M.H.; Abdin, R.; Qadura, M.; Britz-McKibbin, P. Serum Metabolic Signatures of Chronic Limb-Threatening Ischemia in Patients with Peripheral Artery Disease. J. Clin. Med. 2020, 9, 1877. https://doi.org/10.3390/jcm9061877

AMA Style

Azab SM, Zamzam A, Syed MH, Abdin R, Qadura M, Britz-McKibbin P. Serum Metabolic Signatures of Chronic Limb-Threatening Ischemia in Patients with Peripheral Artery Disease. Journal of Clinical Medicine. 2020; 9(6):1877. https://doi.org/10.3390/jcm9061877

Chicago/Turabian Style

Azab, Sandi M., Abdelrahman Zamzam, Muzammil H. Syed, Rawand Abdin, Mohammad Qadura, and Philip Britz-McKibbin. 2020. "Serum Metabolic Signatures of Chronic Limb-Threatening Ischemia in Patients with Peripheral Artery Disease" Journal of Clinical Medicine 9, no. 6: 1877. https://doi.org/10.3390/jcm9061877

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