title: Disruption of mitochondrial quality control in peripheral artery disease: New therapeutic opportunities.
abstract: Peripheral artery disease (PAD) is a multifactorial disease initially triggered by reduced blood supply to the lower extremities due to atherosclerotic obstructions. It is considered a major public health problem worldwide, affecting over 200 million people. Management of PAD includes smoking cessation, exercise, statin therapy, antiplatelet therapy, antihypertensive therapy and surgical intervention. Although these pharmacological and non-pharmacological interventions usually increases blood flow to the ischemic limb, morbidity and mortality associated with PAD continue to increase. This scenario raises new fundamental questions regarding the contribution of intrinsic metabolic changes in the distal affected skeletal muscle to the progression of PAD. Recent evidence suggests that disruption of skeletal muscle mitochondrial quality control triggered by intermittent ischemia-reperfusion injury is associated with increased morbidity in individuals with PAD. The mitochondrial quality control machinery relies on surveillance systems that help maintaining mitochondrial homeostasis upon stress. In this review, we describe some of the most critical mechanisms responsible for the impaired skeletal muscle mitochondrial quality control in PAD. We also discuss recent findings on the central role of mitochondrial bioenergetics and quality control mechanisms including mitochondrial fusion-fission balance, turnover, oxidative stress and aldehyde metabolism in the pathophysiology of PAD, and highlight their potential as therapeutic targets.
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Brazil.
authors.forename: Cintia B
authors.initials: CB
authors.lastname: Ueta
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Brazil.
authors.forename: Katia S
authors.initials: KS
authors.lastname: Gomes
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Brazil.
authors.forename: Márcio A
authors.initials: MA
authors.lastname: Ribeiro
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, USA.
authors.forename: Daria
authors.initials: D
authors.lastname: Mochly-Rosen
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Brazil. Electronic address: jcesarbf@usp.br.
authors.forename: Julio C B
authors.initials: JC
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D058729:Peripheral Arterial Disease / Q000188:drug therapy*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D015427:Reperfusion Injury / Q000188:drug therapy
chemical_list: D004364:Pharmaceutical Preparations
keywords: 4-Hydroxynonenal; Mitochondrial dynamics; Mitochondrial metabolism; Mitophagy; Myocyte; Redox balance