PMID- 32560175
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2077-0383 (Print)
IS  - 2077-0383 (Electronic)
IS  - 2077-0383 (Linking)
VI  - 9
IP  - 6
DP  - 2020 Jun 16
TI  - Serum Metabolic Signatures of Chronic Limb-Threatening Ischemia in Patients with 
      Peripheral Artery Disease.
LID - 10.3390/jcm9061877 [doi]
LID - 1877
AB  - 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 x 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.
FAU - Azab, Sandi M
AU  - Azab SM
AD  - Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON 
      L8S 4M1, Canada.
AD  - Department of Pharmacognosy, Alexandria University, Alexandria 21521, Egypt.
FAU - Zamzam, Abdelrahman
AU  - Zamzam A
AD  - Department of Surgery, St. Michael's Hospital, Toronto, ON M5B 1W8, Canada.
FAU - Syed, Muzammil H
AU  - Syed MH
AUID- ORCID: 0000-0003-4697-5260
AD  - Department of Surgery, St. Michael's Hospital, Toronto, ON M5B 1W8, Canada.
FAU - Abdin, Rawand
AU  - Abdin R
AD  - Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
FAU - Qadura, Mohammad
AU  - Qadura M
AD  - Department of Surgery, St. Michael's Hospital, Toronto, ON M5B 1W8, Canada.
FAU - Britz-McKibbin, Philip
AU  - Britz-McKibbin P
AD  - Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON 
      L8S 4M1, Canada.
LA  - eng
GR  - x/Natural Sciences and Engineering Research Council of Canada/
GR  - x/Genome Canada/
PT  - Journal Article
DEP - 20200616
PL  - Switzerland
TA  - J Clin Med
JT  - Journal of clinical medicine
JID - 101606588
PMC - PMC7355749
OTO - NOTNLM
OT  - critical limb-threatening ischemia
OT  - intermittent claudication
OT  - metabolomics
OT  - peripheral artery disease
OT  - serum
COIS- The authors declare no conflict of interest.
EDAT- 2020/06/21 06:00
MHDA- 2020/06/21 06:01
PMCR- 2020/06/16
CRDT- 2020/06/21 06:00
PHST- 2020/05/08 00:00 [received]
PHST- 2020/05/30 00:00 [revised]
PHST- 2020/06/10 00:00 [accepted]
PHST- 2020/06/21 06:00 [entrez]
PHST- 2020/06/21 06:00 [pubmed]
PHST- 2020/06/21 06:01 [medline]
PHST- 2020/06/16 00:00 [pmc-release]
AID - jcm9061877 [pii]
AID - jcm-09-01877 [pii]
AID - 10.3390/jcm9061877 [doi]
PST - epublish
SO  - J Clin Med. 2020 Jun 16;9(6):1877. doi: 10.3390/jcm9061877.