BACKGROUND: Mitochondrial abnormalities exist in gastrocnemius muscle of people with peripheral artery disease (PAD). Whether abnormalities in mitochondrial biogenesis and autophagy are associated with greater ischemia or walking impairment in PAD is unknown. METHODS AND RESULTS: Protein markers of mitochondrial biogenesis and autophagy and the abundance of mitochondrial electron transport chain complexes were quantified in gastrocnemius muscle biopsies from people with and without PAD. Their 6-minute walk distance and 4-m gait speed were measured. Sixty-seven participants (mean age 65.0 years [±6.8], 16 [23.9%] women, 48 [71.6%] Black) were enrolled, including 15 with moderate to severe PAD (ankle brachial index [ABI] <0.60), 29 with mild PAD (ABI 0.60–0.90), and 23 without PAD (ABI 1.00–1.40). Abundance of all electron transport chain complexes was significantly higher in participants with lower ABI (eg, complex I: 0.66, 0.45, 0.48 arbitrary units [AU], respectively, P trend=0.043). Lower ABI values were associated with a higher LC3A/B II-to-LC3A/B I (microtubule-associated protein 1A/1B-light chain 3) ratio (2.54, 2.31, 2.15 AU, respectively, P trend=0.017) and reduced abundance of the autophagy receptor p62 (0.71, 0.69, 0.80 AU, respectively, P trend=0.033). The abundance of each electron transport chain complex was positively and significantly associated with 6-minute walk distance and 4-m gait speed at usual and fast pace only among participants without PAD (eg, complex I: r=0.541, P=0.008; r=0.477, P=0.021; r=0.628, P=0.001, respectively). CONCLUSIONS: These results suggest that accumulation of electron transport chain complexes in gastrocnemius muscle of people with PAD may be because of impaired mitophagy in the setting of ischemia. Findings are descriptive, and further study in larger sample sizes is needed.
|Journal||Journal of the American Heart Association|
|State||Published - Mar 21 2023|
Bibliographical noteFunding Information:
The work was partly supported by the American Heart Association Strategically Focused Research Network in Vascular Disease (AHA SFRN 18SFRN33900136), Intramural Research Program of the National Institute on Aging, Intramural Research Grants from the Università Cattolica del Sacro Cuore (D1.2020 and D1.2022), and the nonprofit research foundation “Centro Studi Achille e Linda Lorenzon.”
We thank Brian B. Bouverat and Kevin Wu from the Metabolism and Translational Science Core of the Claude D. Pepper Older Americans Independence Center at the University of Florida (Gainesville, FL) for their technical assistance with muscle sample handling and processing. Sources of Funding The work was partly supported by the American Heart Association Strategically Focused Research Network in Vascular Disease (AHA SFRN 18SFRN33900136), Intramural Research Program of the National Institute on Aging, Intramural Research Grants from the Università Cattolica del Sacro Cuore (D1.2020 and D1.2022), and the nonprofit research foundation “Centro Studi Achille e Linda Lorenzon.”.
© 2023 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
- ankle-brachial index
- electron transport chain
- mitochondrial biogenesis
- mtDNA damage
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine