Cigarette smoking and mitochondrial dysfunction in peripheral artery disease

Area of Science:

• Mitochondrial biology
• Vascular medicine
• Skeletal muscle physiology

Background:

• Peripheral artery disease (PAD) is a common circulatory disorder.
• Mitochondrial dysfunction is implicated in PAD pathophysiology.
• The impact of smoking on muscle mitochondria in PAD is not well understood.

Purpose of the Study:

• To investigate the association between cigarette smoking and mitochondrial function in the gastrocnemius muscle of individuals with PAD.
• To compare mitochondrial oxidative capacity and protein expression in smokers versus non-smokers with PAD.

Main Methods:

• Gastrocnemius muscle biopsies were obtained from participants with PAD.
• Mitochondrial oxidative capacity was assessed using respirometry.
• Abundance of key mitochondrial proteins, including VDAC, PGC-1α, and electron transport chain complexes I-V, was quantified via Western blot.

Main Results:

• Smokers with PAD exhibited increased abundance of PGC-1α, VDAC, complex I, and complex III proteins compared to non-smokers.
• Despite higher protein levels, smokers with PAD showed reduced oxidative capacity per VDAC unit.
• No significant differences in overall mitochondrial oxidative capacity were observed between smoking and non-smoking groups within the PAD cohort.

Conclusions:

• Cigarette smoking in PAD may trigger mitochondrial biogenesis as a compensatory mechanism for diminished mitochondrial efficiency.
• The findings suggest a complex interplay between smoking, mitochondrial adaptation, and muscle function in PAD.
• Further longitudinal studies are warranted to confirm these cross-sectional observations.