Khattri Ram B, Kim Kyoungrae, Thome Trace, Salyers Zachary R, O'Malley Kerri A, Berceli Scott A, Scali Salvatore T, Ryan Terence E
Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL 32611, USA.
Division of Vascular Surgery and Endovascular Therapy, University of Florida, Gainesville, FL 32610, USA.
J Clin Med. 2021 Feb 2;10(3):548. doi: 10.3390/jcm10030548.
Chronic limb threatening ischemia (CLTI) is the most severe manifestation of peripheral atherosclerosis. Patients with CLTI have poor muscle quality and function and are at high risk for limb amputation and death. The objective of this study was to interrogate the metabolome of limb muscle from CLTI patients. To accomplish this, a prospective cohort of CLTI patients undergoing either a surgical intervention (CLTI Pre-surgery) or limb amputation (CLTI Amputation), as well as non-peripheral arterial disease (non-PAD) controls were enrolled. Gastrocnemius muscle biopsy specimens were obtained and processed for nuclear magnetic resonance (NMR)-based metabolomics analyses using solution state NMR on extracted aqueous and organic phases and H high-resolution magic angle spinning (HR-MAS) on intact muscle specimens. CLTI Amputation specimens displayed classical features of ischemic/hypoxic metabolism including accumulation of succinate, fumarate, lactate, alanine, and a significant decrease in the pyruvate/lactate ratio. CLTI Amputation muscle also featured aberrant amino acid metabolism marked by elevated branched chain amino acids. Finally, both Pre-surgery and Amputation CLTI muscles exhibited pronounced accumulation of lipids, suggesting the presence of myosteatosis, including cholesterol, triglycerides, and saturated fatty acids. Taken together, these metabolite differences add to a growing body of literature that have characterized profound metabolic disturbance's in the failing ischemic limb of CLTI patients.
慢性肢体威胁性缺血（CLTI）是外周动脉粥样硬化最严重的表现形式。CLTI患者的肌肉质量和功能较差，面临肢体截肢和死亡的高风险。本研究的目的是探究CLTI患者肢体肌肉的代谢组。为实现这一目的，招募了一个前瞻性队列，其中包括接受手术干预的CLTI患者（CLTI术前组）、接受肢体截肢的CLTI患者（CLTI截肢组）以及非外周动脉疾病（非PAD）对照组。获取腓肠肌活检标本，并使用提取的水相和有机相的溶液态核磁共振（NMR）以及完整肌肉标本的高分辨率魔角旋转（HR-MAS）核磁共振对其进行基于代谢组学的分析。CLTI截肢组标本显示出缺血/缺氧代谢的典型特征，包括琥珀酸、富马酸、乳酸、丙氨酸的积累，以及丙酮酸/乳酸比值的显著降低。CLTI截肢组肌肉还具有异常的氨基酸代谢特征，表现为支链氨基酸升高。最后，术前组和截肢组的CLTI肌肉均表现出脂质的明显积累，提示存在肌肉脂肪变性，包括胆固醇、甘油三酯和饱和脂肪酸。综上所述，这些代谢物差异进一步丰富了已有文献，这些文献已描述了CLTI患者缺血肢体功能衰竭时存在的严重代谢紊乱。
