Mitochondrial Bioenergetics in the Metabolic Myopathy Accompanying Peripheral Artery Disease.

Blake B. Rasmussen,Craig Porter,Zulfiqar F. Cheema,Omar Nunez Lopez,Victoria G. Rontoyanni,Grant T. Fankhauser

doi:10.3389/fphys.2017.00141

Abstract

Peripheral artery disease (PAD) is a serious but relatively underdiagnosed and undertreated clinical condition associated with a marked reduction in functional capacity and a heightened risk of morbidity and mortality. The pathophysiology of lower extremity PAD is complex, and extends beyond the atherosclerotic arterial occlusion and subsequent mismatch between oxygen demand and delivery to skeletal muscle mitochondria. In this review, we evaluate and summarize the available evidence implicating mitochondria in the metabolic myopathy that accompanies PAD. Following a short discussion of the available in vivo and in vitro methodologies to quantitate indices of muscle mitochondrial function, we review the current evidence implicating skeletal muscle mitochondrial dysfunction in the pathophysiology of PAD myopathy, while attempting to highlight questions that remain unanswered. Given the rising prevalence of PAD, the detriment in quality of life for patients, and the associated significant healthcare resource utilization, new alternate therapies that ameliorate lower limb symptoms and the functional impairment associated with PAD are needed. A clear understanding of the role of mitochondria in the pathophysiology of PAD may contribute to the development of novel therapeutic interventions.

Highlights

Peripheral artery disease (PAD) is the third leading cause of cardiovascular morbidity after coronary heart disease and stroke (Fowkes et al, 2013)
Diminished skeletal muscle oxidative capacity appears to result from both impaired blood flow and altered mitochondrial respiratory capacity and quality
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Summary

INTRODUCTION

Peripheral artery disease (PAD) is the third leading cause of cardiovascular morbidity after coronary heart disease and stroke (Fowkes et al, 2013). In the first of these studies, mitochondrial respiration was determined in skeletal muscle from 9 patients with advanced PAD (mean ABI, 0.4) and 9 PAD-free individuals (Pipinos et al, 2003) These authors found that ADP stimulated respiration supported by complex I was lower in PAD patients compared to controls, suggesting a quantitative deficit in mitochondrial respiratory capacity in PAD. van Schaardenburgh et al (2016) recently studied both mitochondrial respiratory capacity and coupling control in permeabilized muscle fibers from the gastrocnemius muscle of 11 patients with PAD (mean ABI, 0.65) and 11 PAD-free healthy older adults They found lower mitochondrial respiration supported by complex I but normal complex-IIsupported respiration in PAD vs PAD-free patients, in contrast to the previous findings of Elander et al (1985).

Summary and Future Directions

CONCLUSION