The morphology and network architecture of pericytes in skeletal muscle and their potential involvement in blood flow control

Capillaries are critical coordinators of the microvasculature important in directing blood flow to metabolically active tissue. The architecture of capillary units (CUs) are integral in delivering blood flow to active skeletal muscle fibers. Throughout many tissues capillaries are associated and share a basement membrane with pericytes. In the brain, three types of pericytes have been documented, 1) ensheathing, 2) mesh-type, and 3) thin strand (TS) pericytes; and have been shown to be involved in blood flow control. However, in skeletal muscle the types of pericytes present, their association with capillaries, and their involvement in blood flow control remains unknown. The objective of this study was to determine the morphological and architectural relationship between pericytes and skeletal muscle capillaries. We hypothesized that a) pericytes would be associated with capillaries, and b) that the pericyte ‘network’ would not be similar architecturally to that of the CU. We visualized the pericytes using male and female Tg(Cspg4-DsRed.T1)1Akik/J reporter mice, where NG2 membrane proteins were labeled with red fluorescent protein (RFP). We viewed pericyte architecture in relation to the microvascular network architecture by perfusing the RFP mice with fluorescent dyes that label the vascular endothelial cells. We investigated various skeletal muscles including Gluteus Maximus (GM), Diaphragm (DIA), Soleus (SOL), Extensor Digitorum Longus (EDL), and Cremaster (CRE) to investigate potential fiber type differences. All muscles were excised, pinned at optimal length, and viewed as whole mounts using fluorescent microscopy. We observed that TS pericytes were associated with capillaries. Capillaries were extensively covered by pericytes but did not follow the architecture of the CU. The ratio of endothelial cells (capillaries):TS pericytes in females was, 1.7±0.5:1 in GM, 3.6∓0.8:1 in DIA, 1.5±0.1:1 in EDL and 2.5±0.5: in SOL; and 2.3±0.6:1 in GM, 3.7±0.6:1 in DIA, 2.4±0.2:1 in EDL, 2.5±0.4:1 in SOL, and 1.1±0.1:1 in CRE in males. There were no differences observed in the endothelial cell:pericyte ratio between males and females with the exception of EDL (p<0.05). There were no differences in the endothelial cell:pericyte ratio observed within females, but in males CRE was significantly different from DIA, EDL and SOL but not GM (p<0.05). In conclusion, TS pericytes were associated with capillaries in each of the observed muscles. There appear to be sex based differences in the ratio between capillaries and pericytes. Differences in the ratio between capillaries and pericytes suggest that pericytes do not mirror the architecture of the CU and therefore may not be involved in the coordination of blood flow control in the skeletal muscle. NSERC This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.