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

Author(s)

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

• Document type: Review article
• Source: PHARMACOLOGICAL RESEARCH; v. 115, p. 96-106, JAN 2017.
• Web of Science Citations: 8

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

• FAPESP's process: 15/01759-6 - Aldehyde dehydrogenase 2 profile in peripheral artery disease progression
• Grantee: Márcio Augusto Campos Ribeiro
• Support type: Scholarships in Brazil - Master
• FAPESP's process: 14/15187-1 - Characterization of skeletal muscle satellite cells metabolism and redox balance: role of aldehydes as metabolic sensors
• Grantee: Kátia Maria Gomes Andrade
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/24321-0 - Prior exercise induces cardioprotection against ischemia-reperfusion injury: contribution of the intracellular axis PKCepsilon-ALDH2
• Grantee: Laís Santos Domingues
• Support type: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 12/05765-2 - Contribution of aldehyde dehydrogenase 2 to heart failure development
• Grantee: Julio Cesar Batista Ferreira
• Support type: Research Grants - Young Investigators Grants
• FAPESP's process: 15/20783-5 - Protein quality control in dysfunctional/atrophic skeletal muscle: role of b2-adrenoceptor
• Grantee: Julio Cesar Batista Ferreira
• Support type: Regular Research Grants