Gratl 2021 J Transl Med
|Gratl A, Pesta D, Gruber L, Speichinger F, Raude B, Omran S, Greiner A, Frese JP (2021) The effect of revascularization on recovery of mitochondrial respiration in peripheral artery disease: a case control study. https://doi.org/10.1186/s12967-021-02908-0J|
» Transl Med 19:244. PMID: 34088309 Open Access
Gratl Alexandra, Pesta Dominik, Gruber Leonhard, Speichinger Fiona, Raude Ben, Omran Safwan, Greiner Andreas, Frese Jan Paul (2021) J Transl Med
Abstract: Peripheral arterial disease (PAD) is accompanied by myopathy characterized by mitochondrial dysfunction. The aim of this experimental study was to investigate the effect of revascularization procedures on mitochondrial function in ischemic and non-ischemic muscle.
Muscle biopsies from patients with symptomatic stage IIB/III PAD caused by isolated pathologies of the superficial femoral artery were obtained from muscle regions within the chronic ischemic muscle (gastrocnemius) and from non-ischemic muscle (vastus lateralis) before and 6 weeks after invasive revascularization. High-resolution respirometry was used to investigate mitochondrial function and results were normalized to citrate synthase activity (CSA). Results are given in absolute values and fold over basal (FOB).
Respiratory states (OXPHOS (P) and electron transfer (E) capacity) normalized to CSA decreased while CSA was increased in chronic ischemic muscle after revascularization. There were no changes in non-ischemic muscle. The FOB of chronic ischemic muscle was significantly higher for CSA (chronic ischemic 1.37 (IQR 1.10-1.64) vs. non-ischemic 0.93 (IQR 0.69-1.16) p = 0.020) and significantly lower for respiratory states normalized to CSA when compared to the non-ischemic muscle (P per CSA chronic ischemic 0.64 (IQR 0.46-0.82) vs non-ischemic 1.16 (IQR 0.77-1.54) p = 0.011; E per CSA chronic ischemic 0.61 (IQR 0.47-0.76) vs. non-ischemic 1.02 (IQR 0.64-1.40) p = 0.010).
Regeneration of mitochondrial content and function following revascularization procedures only occur in muscle regions affected by malperfusion. This indicates that the restoration of blood and oxygen supply are important mediators aiding mitochondrial recovery. • Keywords: Intermittent claudication, Mitochondrial function, Mitochondrial respiration, PAD, Peripheral arterial disease, Revascularization • Bioblast editor: Plangger M • O2k-Network Lab: DE Cologne Pesta D
Labels: MiParea: Respiration
Stress:Ischemia-reperfusion Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET Pathway: F, N, NS HRR: Oxygraph-2k