Critical Limb Ischaemia Exacerbates Mitochondrial Dysfunction in ApoE–/– Mice Compared with ApoE+/+ Mice, but N-acetyl Cysteine still Confers Protection
| Autor: | Charline Delay, Anne Lejay, Nabil Chakfe, Anne-Laure Charles, Bernard Geny, Isabelle Georg, Fabien Thaveau, Samy Talha, Fabienne Goupilleau |
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| Přispěvatelé: | Mitochondrie, stress oxydant et protection musculaire (MSP), Université de Strasbourg (UNISTRA) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Apolipoprotein E
medicine.medical_specialty Antioxidant Mice Knockout ApoE Critical Illness medicine.medical_treatment [SDV]Life Sciences [q-bio] Ischemia chemistry.chemical_element Hyperlipidemias 030204 cardiovascular system & hematology 030230 surgery Mitochondrion Calcium medicine.disease_cause Antioxidants Peripheral Arterial Disease 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Muscle Skeletal chemistry.chemical_classification Reactive oxygen species business.industry medicine.disease Acetylcysteine Mitochondria Muscle Disease Models Animal Oxidative Stress Endocrinology chemistry Surgery Reactive Oxygen Species Cardiology and Cardiovascular Medicine business Oxidative stress Cysteine |
| Zdroj: | European Journal of Vascular and Endovascular Surgery European Journal of Vascular and Endovascular Surgery, Elsevier, 2019, 58, pp.576-582. ⟨10.1016/j.ejvs.2019.03.028⟩ |
| ISSN: | 1078-5884 |
| Popis: | Objectives The current study was performed in order to determine the influence of hypercholesterolaemia on critical limb ischaemia (CLI) and whether targeting oxidative stress by antioxidant therapies such as N-acetyl cysteine (NAC), considered to be a direct scavenger of reactive oxygen species, could confer muscle protection. Methods Apolipoprotein E (ApoE)–/– mice (n = 9, 29 weeks old) and their genetic controls ApoE+/+ mice (n = 9, 29 weeks old) were submitted to sequential right femoral and iliac ligations; the left limb served as control. ApoE+/+ mice were divided into two groups: Group 1 (n = 4) and Group 2 (n = 5); as well as ApoE–/– mice: Group 3 (n = 3), and Group 4 (n = 6). NAC treatment was administered to Groups 2 and 4 in drinking water. Mice were sacrificed on Day 40 and gastrocnemius muscles were harvested to study mitochondrial respiration by oxygraphy, calcium retention capacity by spectrofluorometry, and production of reactive oxygen species by electron paramagnetic resonance. Results CLI associated with ApoE deficiency resulted in more severe mitochondrial dysfunction: maximum oxidative capacity and calcium retention capacity were decreased (−42.9% vs. −25.1%, p = .010; and −73.1% vs. −40.3%, p = .003 respectively) and production of reactive oxygen species was enhanced (+63.6% vs. +41.4%, p = .03) in ApoE–/– mice compared with ApoE+/+ mice respectively. Antioxidant treatment restored oxidative capacity, calcium retention capacity and decreased production of reactive oxygen species in both mice strands. Conclusions In this small murine study, hypercholesterolaemia exacerbated mitochondrial dysfunction, as clinically expected; but antioxidant therapy appeared protective, which is counter to clinical experience. Further work is clearly needed. |
| Databáze: | OpenAIRE |
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