Associations of Poly (ADP-Ribose) Polymerase1 abundance in calf skeletal muscle with walking performance in peripheral artery disease.

Abstract

This study investigated associations of markers of oxidative stress and mitochondrial function in calf muscle biopsies with walking performance in people with and without lower extremity peripheral artery disease (PAD). Participants with PAD (ankle-brachial index (ABI) <0.90) and without PAD (ABI: 0.90-1.50) underwent calf muscle biopsy and measurement of 6-min walk and four-meter walking velocity. PARP1 (Poly (ADP-Ribose) Polymerase 1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), silent information regulator 1 (SIRT1) and 4-hydroxynonenal (4HNE) expression were measured in calf muscle using western blot. Among 15 participants with PAD mean age: 66.8years (standard deviation (SD): 6.4) and six without PAD (age: 64.4years, SD: 5.9), mean PARP1-abundance in calf muscle was 1.16±0.92AU and 0.96±0.38AU, respectively (P=0.61). Among participants with PAD after adjustment with ABI, a greater abundance of PARP1 was associated with poorer 6-min walking distance (r=-0.65, P=0.01), usual-paced 4-m walking velocity (r=-0.73, P=0.003) and slower fast-paced four-meter walking velocity (r=-0.51, P=0.07). Among participants with PAD, ABI was not associated with PARP1 abundance in calf muscle (r=0.02, P=0.93). Among participants without PAD, skeletal muscle PARP1 abundance was not significantly associated with 6-min walk distance (r=-0.58; P=0.22), usual-paced walking velocity (r=-0.26; P=0.62), or fast-paced walking velocity (r=-0.21; P=0.69), perhaps due to lack of statistical power. There were no associations of remaining calf muscle measures with walking performance. These findings are consistent with the hypothesis that calf skeletal muscle characteristics are related to walking performance, independently of severity of lower extremity arterial obstruction in people with PAD.