title: Chronology of mitochondrial and cellular events during skeletal muscle ischemia-reperfusion.
abstract: Peripheral artery disease (PAD) is a common circulatory disorder of the lower limb arteries that reduces functional capacity and quality of life of patients. Despite relatively effective available treatments, PAD is a serious public health issue associated with significant morbidity and mortality. Ischemia-reperfusion (I/R) cycles during PAD are responsible for insufficient oxygen supply, mitochondriopathy, free radical production, and inflammation and lead to events that contribute to myocyte death and remote organ failure. However, the chronology of mitochondrial and cellular events during the ischemic period and at the moment of reperfusion in skeletal muscle fibers has been poorly reviewed. Thus, after a review of the basal myocyte state and normal mitochondrial biology, we discuss the physiopathology of ischemia and reperfusion at the mitochondrial and cellular levels. First we describe the chronology of the deleterious biochemical and mitochondrial mechanisms activated by I/R. Then we discuss skeletal muscle I/R injury in the muscle environment, mitochondrial dynamics, and inflammation. A better understanding of the chronology of the events underlying I/R will allow us to identify key factors in the development of this pathology and point to suitable new therapies. Emerging data on mitochondrial dynamics should help identify new molecular and therapeutic targets and develop protective strategies against PAD.
authors.affiliation: University of Strasbourg, Fédération de Médecine Translationelle, EA 3072, Strasbourg, France; Department of Physiology and Functional Explorations, Thoracic Pathology Unit, Centre Hospitalier Régional Universitaire de Strasbourg, Strasbourg, France; sparadis@unistra.fr.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Paradis
authors.affiliation: University of Strasbourg, Fédération de Médecine Translationelle, EA 3072, Strasbourg, France; Department of Physiology and Functional Explorations, Thoracic Pathology Unit, Centre Hospitalier Régional Universitaire de Strasbourg, Strasbourg, France;
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Charles
authors.affiliation: University of Strasbourg, Fédération de Médecine Translationelle, EA 3072, Strasbourg, France; Department of Physiology and Functional Explorations, Thoracic Pathology Unit, Centre Hospitalier Régional Universitaire de Strasbourg, Strasbourg, France;
authors.forename: Alain
authors.initials: A
authors.lastname: Meyer
authors.affiliation: University of Strasbourg, Fédération de Médecine Translationelle, EA 3072, Strasbourg, France; Department of Physiology and Functional Explorations, Thoracic Pathology Unit, Centre Hospitalier Régional Universitaire de Strasbourg, Strasbourg, France; Department of Vascular Surgery and Kidney Transplantation, Centre Hospitalier Régional Universitaire de Strasbourg, Strasbourg, France; and.
authors.forename: Anne
authors.initials: A
authors.lastname: Lejay
authors.affiliation: Department of Medicine and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: James W
authors.initials: JW
authors.lastname: Scholey
authors.affiliation: University of Strasbourg, Fédération de Médecine Translationelle, EA 3072, Strasbourg, France; Department of Vascular Surgery and Kidney Transplantation, Centre Hospitalier Régional Universitaire de Strasbourg, Strasbourg, France; and.
authors.forename: Nabil
authors.initials: N
authors.lastname: Chakfé
authors.affiliation: University of Strasbourg, Fédération de Médecine Translationelle, EA 3072, Strasbourg, France; Department of Physiology and Functional Explorations, Thoracic Pathology Unit, Centre Hospitalier Régional Universitaire de Strasbourg, Strasbourg, France;
authors.forename: Joffrey
authors.initials: J
authors.lastname: Zoll
authors.affiliation: University of Strasbourg, Fédération de Médecine Translationelle, EA 3072, Strasbourg, France; Department of Physiology and Functional Explorations, Thoracic Pathology Unit, Centre Hospitalier Régional Universitaire de Strasbourg, Strasbourg, France;
authors.forename: Bernard
authors.initials: B
authors.lastname: Geny
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D058729:Peripheral Arterial Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D018836:Inflammation Mediators
keywords: ischemia-reperfusion; mitochondria; oxidative stress; peripheral artery disease; skeletal muscle