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Table 4 Experimental evidence with manifestations of atherosclerosis in skeletal muscle

From: Crossroads between peripheral atherosclerosis, western-type diet and skeletal muscle pathophysiology: emphasis on apolipoprotein E deficiency and peripheral arterial disease

Reference

Intervention

Findings

[195]

♂ ApoE-/-, Ldlr-/- and WT (20wks); ND

↑ arterial pressure& Insulin resistance in Ldlr-/-; ↔ endothelial vasodilation and VSMC reactivity in skeletal muscle arterioles; ↓ NO bioavailability in ApoE-/-

[194]

♂ ApoE-/-, Ldlr-/- and WT (12–13 and 22–23 wks); ND

↓ capillary density in gastrocnemius of ApoE--/- from 12wks and in Ldlr-/- from 22wks; ↑ plasma oxidative stress and inflammatory markers in ApoE-/- and Ldlr-/-; ↑ wall:lumen ratio in Ldlr-/-

[198]

♂ ApoE-/- and WT (18wks);

HFD (21% w/w) or ND for 12wks

↓ inflammation in AT and skeletal muscle of ApoE-/- HFD; ↓ Akt phosphorylation in AT and skeletal muscle of WT HFD; ↑ crown like structures in WT HFD; ↓ dietary lipid incorporation in adipose tissue, skeletal muscle and liver in ApoE-/- HFD; No oxidative stress in adipose tissue; ↑ TGs in skeletal muscle of WT HFD

[199]

♂ ApoE-/- and WT (16wks); HFD (60% v/v fat) or ND for 9wks

↑ H2O2 in liver and muscle of ApoE-/- ND and HFD; ↑ H2O2 in AT of ApoE-/- HFD; ↑ IL-6 in adipose tissue of WT HFD and ApoE-/-; ↑ TNFα of WT HFD and ApoE-/- HFD; ↑ crown like structures in adipocytes of ApoE-/- HFD

[215]

♀ ApoE-/- (8-10months); Femoral artery ligation; ND

Hyperaemic response to treadmill exercise similar to human studies on PAD

[211]

ApoE-/- (19-21wks); Iliac artery ligation; ND

↓ blood flow in the ischemic hindlimbs; ↑ capillarisation only in quadriceps; ↑ fibre atrophy; ↑ of glucose uptake and pro-inflammatory macrophages and T cells at early ischemic stages

[217]

♀ ApoE-/- and WT (8-10months); Hindlimb ischemia; ND

↓ myogenin levels in 7d post and ↑ MCP-1 levels at 14d post ischemia/reperfusion in ApoE-/; Delayed skeletal muscle regeneration

[218]

♂ and ♀ ApoE-/- and WT (18-26wks); Notexin injury; ND

↑ fat lipid deposition and calcification; ↓ fibre size; Delayed skeletal muscle regeneration

[216]

♀ ApoE-/- and WT (16-8wks); ND for WT and WD (1.25% cholesterol, 15% w/w fat) in ApoE-/- for 10wks; Hindlimb ischemia (removal of femoral artery and all major collateral branches) and subsequent treatment for 21d with miR-150 mimic peptide

↓ blood perfusion in ApoE-/- vs WT that improved with the miR-150 peptide; ↑ ambulatory impairment in ApoE-/- vs WT that decreased with the miR-150 peptide; ↓ capillary density in ApoE-/- vs WT that improved with the miR-150 peptide; ↓ number and functional activities of PACs in ApoE-/- vs WT that improved with the miR-150 peptide

[221]

♀ Ldlr-/- (22wks) and ApoE-/- (36wks); Hindlimb ischemia (double ligation of femoral artery) and subsequent treatment with IFNAR1 Mab or IgG isotype (control); WD (16% w/w fat, 0.15% cholesterol) in Ldlr-/- for 8wks and for 24wks in ApoE-/-

↑ hindlimb perfusion restoration in Ldlr-/- treated with IFNAR1 Mab vs Ldlr-/-; ↔ capillary density in Ldlr-/- treated with IFNAR1 Mab vs Ldlr-/-; ↔ atherosclerotic burden and lesion characteristics in Ldlr-/- treated with IFNAR1 Mab vs Ldlr-/-; ↑ hindlimb perfusion restoration in ApoE-/-treated with IFNAR1 Mab vs ApoE-/-; ↓ number of arterioles in ligated limb of ApoE-/- treated with IFNAR1 Mab and ApoE-/- vs sham side of ApoE-/- treated with IFNAR1 Mab and ApoE-/- respectively; ↔ atherosclerotic burden and lesion characteristics in ApoE-/- treated with IFNAR1 Mab vs ApoE-/-

[220]

♂ Ldlr-/-, Ldlr-/-/CCR7-/-, WT (8-12wks); Hindlimb ischemia with electrocoagulation of femoral artery

Blood flow recovery at 7d for WT, at 10d for LDLR-/- and in Ldlr-/-/CCR7-/- was not fully recovered after 21d; ↔ number of dendritic cells and T lymphocytes in spleen, lymph nodes and blood in Ldlr-/- vs WT

[219]

♂ Ldlr-/- and WT (18wks); WT on ND and Ldlr-/- on HFD (15.1% fat, 1.25% cholesterol) for 12wks; Iliac and femoral artery ligation at 18wks; Subsequent treatment with heparin, bFGF, heparin and bFGF or no treatment for 4wks

Blood flow of ischemic limb: ↑ in heparin treated, ↑↑ in bFGF treated and ↑↑ in bFGF plus heparin in WT vs WT not treated and in Ldlr-/-: ↔ in heparin, in bFGF and not treated vs ↑ in bFGF plus heparin; Blood perfusion in ischemic limb: ↓ in not treated Ldlr-/- vs WT not treated; Mature vessels of ischemic limb: ↑ in heparin treated, ↑ in bFGF treated, ↑ in bFGF plus heparin in WT vs WT not treated and Ldlr-/- : ↑ in heparin, ↑ in bFGF and ↑↑ bFGF plus heparin vs Ldlr-/-not treated

  1. Abbreviations and Symbols: Akt Protein kinase B, ApoE -/- Apolipoprotein E knockout, AT Adipose Tissue, bFGF basic Fibroblast Growth Factor, CCR7 Chemokine C-C receptor type 7, HFD High-fat Diet, H 2 O 2 Hydrogen Peroxide, IFNAR1 Interferon α/β receptor type 1, IL-6 Interleukin 6, Ldlr -/- Low-Density Lipoprotein Receptor knockout, Mab Monoclonal Antibody, MCP1 monocyte chemotactic protein 1, ND Normal Diet (chow diet), NO Nitric Oxide, PACs Bone marrow derived proangiogenic cells, PAD Peripheral Arterial Disease, TBARS Thiobarbituric acid reactive substances, TNFa Tumor necrosis factor a, VSMC vascular smooth muscle cells, WD Western-type diet, WT wild type; ↔ similar, ↓ decrease, ↑ increase; ♂: male; ♀: female; All strains WT, ApoE-/- and LDLR-/- are on a C57Bl/6 background