Abstract 3024: Mitochondrial Volume Abnormalities In Gastrocnemius Muscle Of Patients With Peripheral Artery Disease

Abstract

Background: The mechanisms of claudication in patients with peripheral artery disease (PAD) are poorly understood. Mitochondria are responsible for ATP production during aerobic conditions but may become structurally impaired in patients with chronic ischemia and PAD. Research Question: Are mitochondrial volumes different in patients with PAD compared with age-matched controls? Aims: To better understand mitochondrial abnormalities and ultrastructure in patients with PAD. Methods/Approach: Patients with PAD (defined as ABI <0.85) and age-matched controls (ABI 1.00-1.40) were recruited and underwent gastrocnemius muscle biopsy. Muscle samples were collected in optimal cutting temperature compound. Mitochondria were labeled with cytochrome oxidase IV antibody and Cy3 fluorescence secondary antibody and images were rendered in three dimensions using structured illumination microscopy to quantify mitochondrial size, content, and morphology. Comparisons were done with a Mann-Whitney U test. Results/Data: Forty-eight subjects (median [IQR] age 66.5 [59.0, 74.0] years, 32 (66.7%) male) were recruited and underwent gastrocnemius muscle biopsy, including 16 controls and 32 with PAD. The largest singular mitochondrial volume was greater in those with PAD (22.6 vs. 4.2μm 3 , p=0.01, Figure 1A) but the median mitochondrial volume was smaller (0.07 vs. 0.01μm 3 , p=0.03, Figure 1B). While no control mitochondria were larger than 7.2μm 3 , 1% of mitochondria in patients with PAD were larger than 10μm 3 (Figure 1C). There was no difference in the total mitochondrial volume or content between PAD and controls. Conclusion: Patients with PAD have larger maximum but smaller median mitochondria sizes in the gastrocnemius muscle, suggesting greater heterogeneity of mitochondrial size in those with PAD. The changes in mitochondrial morphology may result in mitochondrial inefficiency and an impaired compensatory response in the setting of chronic ischemia from PAD.