Azab Sandi M, Zamzam Abdelrahman, Syed Muzammil H, Abdin Rawand, Qadura Mohammad, Britz-McKibbin Philip
Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4M1, Canada.
Department of Pharmacognosy, Alexandria University, Alexandria 21521, Egypt.
J Clin Med. 2020 Jun 16;9(6):1877. doi: 10.3390/jcm9061877.
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 ( = 18) and intermittent claudication (IC, = 20). Compared to the non-PAD controls ( = 20), PAD patients had lower serum concentrations of creatine, histidine, lysine, oxoproline, monomethylarginine, as well as higher circulating phenylacetylglutamine ( < 0.05). Importantly, CLTI cases exhibited higher serum concentrations of carnitine, creatinine, cystine and trimethylamine--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 ( = ±0.24-0.59, < 0.05), whereas the ratio of stearic acid to carnitine, and arginine to propionylcarnitine differentiated CLTI from IC with good accuracy ( = 0.87, = 4.0 × 10). 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.
外周动脉疾病（PAD）的特征是下肢血管发生动脉粥样硬化性狭窄，导致老年人出现缺血性肌肉疼痛。一些患者会进展为晚期慢性肢体威胁性缺血（CLTI），长期生存率较低。在此，我们进行了血清代谢组学研究，以揭示PAD病理生理学机制，这可能有助于改善其诊断和对CLTI的预后评估，作为踝臂指数（ABI）和临床表现的补充。通过多段进样-毛细管电泳-质谱联用（MSI-CE-MS）对年龄和性别匹配、非糖尿病的PAD参与者的血清进行非靶向代谢物谱分析，这些参与者根据卢瑟福分类法被招募并临床分层为CLTI（n = 18）和间歇性跛行（IC，n = 20）。与非PAD对照组（n = 20）相比，PAD患者血清中肌酸、组氨酸、赖氨酸、氧脯氨酸、单甲基精氨酸的浓度较低，而循环中的苯乙酰谷氨酰胺浓度较高（P < 0.05）。重要的是，与匹配良好的IC患者相比，CLTI患者血清中肉碱、肌酐、胱氨酸和氧化三甲胺的浓度较高，而循环脂肪酸浓度较低。大多数与PAD进展相关的血清代谢物也与ABI相关（r = ±0.24 - 0.59，P < 0.05），而硬脂酸与肉碱的比值以及精氨酸与丙酰肉碱的比值能够很好地区分CLTI和IC（AUC = 0.87，P = 4.0 × 10⁻⁴）。这项工作为PAD进展提供了新的生化见解，有助于早期检测和监测可能需要外周血管干预以预防截肢和过早死亡的高危患者。
