Disruption of mitochondrial quality control in peripheral artery disease: New therapeutic opportunities

Autor(es)

Ueta, Cintia B. ; Gomes, Katia S. ; Ribeiro, Marcio A. ; Mochly-Rosen, Dania ; Ferreira, Julio C. B.

• Tipo de documento: Artigo de Revisão
• Fonte: PHARMACOLOGICAL RESEARCH; v. 115, p. 96-106, JAN 2017.
• Citações Web of Science: 8

Resumo

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. (C) 2016 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 12/05765-2 - Contribuição da enzima aldeído desidrogenase 2 na progressão da insuficiência cardíaca
• Beneficiário: Julio Cesar Batista Ferreira
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
• Processo FAPESP: 15/20783-5 - Controle de qualidade de proteína na disfunção/atrofia muscular esquelética: papel do receptor ²2- adrenérgico
• Beneficiário: Julio Cesar Batista Ferreira
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/15187-1 - Caracterização do metabolismo energético e balanço redox das células satélites musculares esqueléticas: papel do aldeído como sinalizador metabólico
• Beneficiário: Kátia Maria Gomes Andrade
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/24321-0 - Papel cardioprotetor do exercício físico na isquemia/reperfusão: possível contribuição do eixo intracelular PKCepsilon-ALDH2
• Beneficiário: Laís Santos Domingues
• Linha de fomento: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 15/01759-6 - Participação da enzima aldeído desidrogenase 2 na progressão da doença arterial periférica
• Beneficiário: Márcio Augusto Campos Ribeiro
• Linha de fomento: Bolsas no Brasil - Mestrado