Pericytes are contractile cells that can control capillary blood flow. Although well studied in other organs, little is known about pericytes in muscle microvasculature and how muscle pericytes are impacted by type 2 diabetes (T2D). Our aim was to comprehensively characterise pericytes in healthy and T2D muscles.
Male transgenic mice (Tg(Cspg4-DsRed.T1)1Akik/J; reporter mouse where pericytes express DsRed protein) were allocated to either control diet (6% fat, n=8) or high fat diet (HFD; 23% fat, n=7) for 17 weeks. In weeks 3-5, HFD-fed mice were treated with streptozotocin (STZ; 250-300mg/kg infused using osmotic mini pumps over 14 days) to induce moderate hyperglycemia. In week 17, mice were euthanised and cardiac perfused with PBS, followed by 4% paraformaldehyde. The tibialis anterior, gastrocnemius and plantaris were excised, processed for immunohistochemistry and imaged using confocal microscopy.
Compared with control mice, T2D mice were obese (29.0±2.7 vs 37.1±5.5 g, p=0.009) and had elevated fasting glucose (9.4±0.6 vs 18.9±5.4 mmol/L, p=0.003). In healthy muscles, pericyte density was consistent relative to capillary length (gastrocnemius=12.0±4.4 cells/mm; plantaris=11.1±3.2 cells/mm; tibialis=9.0±2.7 cells/mm) and pericyte’s covered ~ 95% of all capillary length. Although T2D did not change capillary density, pericyte density in muscles was reduced by ~30% (9.0±2.7 vs 6.09±3.40 cells/mm, p=0.02). Next, we assessed pericyte morphology and discovered that pericyte extensions that run along capillaries had multiple swellings and appeared to be fragmenting in T2D muscles, regardless of muscle type.
In summary, skeletal muscle microvasculature is almost completely covered by pericytes and their complex network of cellular processes. In T2D, muscle pericyte density is reduced and the cellular processes appear swollen and damaged. Given pericytes are regulators of capillary blood flow in other organs, our work suggests that muscle pericytes may have important physiological functions to control capillary blood flow and therefore muscle metabolism in health and T2D.