Table 2 Skeletal muscle deficits in patients with peripheral arterial disease

[10]

62 ± 2 yr; IC > 1y; ABI: 0.58 ± 0.03; GT test → muscle biopsy of gastrocnemius

↓ maximal walking time, peak power, ABI, VO₂ in PAD limbs; ↓ type I ↑ IIA fibres; ↔ IIB; 9% ↓ CSA; ↔ Capillary to fibre ratio; ↔ Muscle glycogen

[151]

68–71 yr; ABI: 0.64 ± 0.04; ↑ Smokers in PAD group; GT test → muscle biopsy of gastrocnemius

↓ Mitochondrial activity of complex I and III;

[27]

IC group with ABI = 0.35 ± 0.06; CLI group with ABI = 0.27 ± 0.05; Muscle biopsy of Gastrocnemius; More male in all groups; ↑ smokers, diabetes, hypertension in both PAD groups; ↓ obese in both PAD groups

Features of progressive muscle degeneration (i.e. myofibre atrophy, loss of the polygonal fibre shape, nuclear clumps, ↑ central nucleation, fibre vacuolization, target lesions, myofibre regeneration, myofibre necrosis and fibrosis and replacement of muscle by adipose tissue;

[190]

CLI; Study of popliteal arteries after amputation

↑ ET-1 plasma levels by 4-fold and ‘locally’ in femoral artery; ↑ atherosclerosis in popliteal arteries; ET-1 & receptors ET_A ET_B were associated with the luminal endothelium, ECs of the adventitial vasa vasorum and neural microvessels. ETA receptor similar in distribution to ET-1, co-localising with macrophages.

[148]

Diabetes, Hypercholesterolaemia,

Hypertension; 76 yrs old; Grade III (intermediate), IV and V (advanced) lesions; Femoral artery samples

↑ inflammation in both stages, with different gene expression patterns; ↑ proteolysis and anti-proliferation markers & ↓ cell metabolism, catabolism in intermediate stage; ↑ vascular extracellular matrix markers & ↓ markers of protein folding, apoptosis, protein modification in advanced lesions

[150]

ABI = 0.55 ± 0.21; Age & sex matched; Diabetes, CAD, Dyslipidaemia, Hypertension; ↑ Smokers in PAD group; Muscle biopsy of gastrocnemius

↑ desmin by 21.5%; Abnormal morphology of myofibres with ↓ CSA, Negative correlation between CSA, morphology and desmin content; ↓ mitochondrial respiration from complex I and IV with irregular distribution; Negative correlation between isometric plantarflexor strength and desmin

[6]

Sex & Aged Matched; Type I Diabetes,

CAD, Dyslipidaemia, Hypertension; ↑ Smokers in PAD groups Fontaine stage II (ABI = 0.53 ± 0.04) and IV (ABI = 0.25 ± 0.04); Muscle biopsy of gastrocnemius

↑ 25% of carbonyl content in all fibre types, mostly in type II fibres for all PAD patients; ↓ CSA; ↑ carbonyl content in PAD-IV vs. PAD-II patients; ↑ damage in type II fibres in PAD-II, whereas in PAD-IV type II and I/II had equal damage; Shift from type II to type I for both stages;

[141]

Age & Sex Matched; ↑ Smokers, Diabetes, CAD, Hypertension & Dyslipidaemia in PAD group; Advanced PAD ABI = 0.34 ± 0.05; Muscle biopsy of gastrocnemius

↓ activity of complexes I, III and IV; ↓ mitochondrial respiration; ↓ protein expression of MnSOD; ↑ Catalase, GPx activity; ↔ CuSOD activity; ↑ Carbonyl content, Lipid hydroperoxides and 4-HNE adducts; ↔ Mitochondrial number;

[155]

Mean ABI = 0.4;

Lower extremities operations

↔ mitochondrial respiration in baseline; ↓ mitochondrial respiration state 3 and 4

[9]

Age & sex matched; ↑ CAD & Hypertension in PAD groups; matched for smoking, myocardial infraction, stroke, renal insufficiency, obesity, dyslipidaemia; Fontaine Stage II, III and IV; ABI = 0.34 ± 0.24; Lower extremities operations

↑ carbonyl content and 4-HNE adducts in line with advanced stages of disease; ↓ myofibre CSA; ↑ oxidative damage

[192]

Age & Sex Matched; ABI = 0.6 ± 0.18; ↑ smokers and statin treatment in PAD group; Gardner Protocol; Muscle Biopsy of gastrocnemius

↑ apoptosis of endothelial cells in myofibres; ↑ caspase 3 expression;

[288]

Age matched; ABI < 0.9 for PAD patients; Smokers, non-diabetic; Muscle biopsy of gastrocnemius

↓ capillary density in gastrocnemius of PAD patients associated with ↓ VO_2max, peak walking time and claudication onset time

[183]

Age & Sex Matched; Diabetic and smokers in both CLI and healthy control group; Muscle biopsy of gastrocnemius in CLI and control group followed by amputation in CLI group

↑ capillary density and capillary to myofibre ratio in gastrocnemius of CLI patients; abnormal structure of the capillaries in CLI group

[162]

ABI = 0.50 ± 0.17; Smokers, non-diabetic; Muscle biopsy of Gastrocnemius

↑ mtDNA deletion (4977 bp) deletion in both limbs but ↑↑ in the affected limb; ↑ other mtDNA deletions

[184]

Sex Matched; ↑ Age in PAD group; ABI = 0.64 ± 0.2; Muscle biopsy of gastrocnemius after exercise

↔ VEGFA concentration; ↔ VEGF₁₆₅b; ↔ VEGFR1 concentration; ↓ capillaries in IC

[182]

Age matched; only male; CAD, Dyslipidaemia, Diabetes; Fontaine stage II-IV; ABI = 0.31 ± 0.25; Muscle biopsy of Gastrocnemius

↑ FoxO1 protein levels negatively correlated with ABI

↔ FoxO3a levels; ↑ p27^KIP1 and THSB1

[147]

Aged matched; ↑ hypercholesterolaemia, smokers and male in PAD group; Fontaine stage III and IV; femoral and popliteal arteries

↑ serum PON1 and CCL2; ↑ thicker tunica intima/tunica media ratio in femoral arteries; ↑ calcium deposits in the media; ↑ PON1, PON3, CD68 (mainly in intima), CCL2 and its receptors DARC, CCBP2 not CCR2 in affected arteries

[142]

Fontaine stage IIa and IIb

↑ serum YKL-40 in PAD patients

[163]

Age & Gender Matched; ↑ hypertension in PAD group; ABI = 0.73 ± 0.14;

↓ capillary density and ↔ capillary/fibre ratio, CSA of fibres; ↑ thickening in basement membrane of lumina; ↓ volume of mitochondria

[143]

PAD with Fontaine stage III and IV

Correlation of PAD and serum cytokines for VEGF, CCL2 and TNFα

[144]

Only PAD patients with ABI = 0.72 ± 0.24 (no control group)

↑ gait impairment that correlated with hsCRP and ICAM-1

[191]

PAD-II (Fontaine stage II, ABI = 0.55 ± 0.22) and PAD-IV (stage IV, ABI = 0.22 ± 0.13) vs control group; Gender matched; Age matched only PAD-II vs control

↑ 3.5-fold in PAD-II and ↑ 8-fold in PAD-IV of TGFβ-1 vs Control; Correlation of collagen density and stage of PAD with TGFβ-1; TGFβ-1 was expressed only by sub-endothelial SMCs and associated with accumulation of fibroblasts and collagen deposition

[264]

PAD Fontaine Stage IIb vs control group;

↔ mRNA level and dialysate VEGF but ↓ protein in PAD vs control; ↔ mRNA levels of VEGFR-2, TSP1 and eNOS; ↑ dialysate of TSP1

[186]

PAD with/without CAD and control group; PAD patients with either IC (70%) or CLI (27%); Age/gender matched

↓↓ in PAD with/without CAD and ↓ in PAD with CAD of flow-mediated dilation and reactive hyperaemia

[132]

CLI; Amputated limbs

↑ calcification of media; lesions lacked of lipids and inflammatory cells, with atherosclerosis being present in less than 25%; Majority had type V, I and II lesions

[161]

Patients with IC and control group; ↑ dyslipidaemia, hypertension, CAD; age matched;

↓ glucose uptake from calf muscle in IC patients; glucose uptake correlates with whole body insulin resistance (with/without diabetes) and not ABI

[133]

PAD patients with IC and CLI (41%);

Majority had type V-VII plaques in femoral arteries; Type of lesions did not correlate with age, sex, diabetes and clinical stage; ↑ of inflammatory cells in lesions of CLI vs IC; No correlation between calcification and clinical stage; Correlation of SMCs and collagen deposition

[154]

PAD patients with IC (ABI = 0.63 ± 0.16) and control group; Age/gender matched; Muscle biopsy from Gastrocnemius

Heterogeneity in fibre type distribution in PAD; ↔ capillary density that doesn’t correlate with fibre type; ↓ SDH and COX-1 activity in myofibres due to ↑ autophagy of the intermyofibrillar mitochondria