Abstract Body: Introduction Peripheral artery disease (PAD) is characterized by atherosclerosis in the lower extremities. Supervised exercise therapy (SET) is the primary treatment to improve symptoms. We believe that satellite cells (SCs) mediate recovery during SET. SCs are skeletal muscle stem cells that repair muscle when activated by stimuli such as exercise. We hypothesize that their adjacency to skeletal muscle capillaries allows activated SCs to secrete angiogenic cues inducing collateral vessels. However, 40 percent of PAD patients are affected by hyperglycemia and diabetes which impair muscle cells including satellite cells. The current SET protocol is walking training (WT), however diabetic patients are suggested to engage in resistance training (RT) to combat the effects of hyperglycemia. Thus, our study investigates SCs' response to hyperglycemia and exercise in terms of SC number, differentiation, and angiogenesis secretome.
Methods: In vitro, we determined the effects of hyperglycemia on SCs number, secretome and angiogenic potential using ki67 staining, multiplex protein assays, and cell migration assays in response to culture under varied glucose levels. To investigate the effects of hyperglycemia and exercise on SCs, WT and db/db diabetic mice underwent resistance (ladder climbing, LC) or aerobic (running, RT) training. We identified changes in cell number and secretome using flow cytometry, histology. and a multiplex protein assay (MPA).
Results & Conclusion Migration increased with SC conditioned media for both MASMs (CM,38.09 ± 27, Control, 12.52 ± 12.74) and MAECs (CM, 119.75 ± 70, Control, 29.7 ± 11.75) (n=8, *p<0.05). Variable glucose concentration in SC growth media, resulted in differential SC secretion that resulted in increased vascular cell migration in both low (2mM, 30% FBS) (110.5 ± 25.92) and high glucose (19Mm, 30% FBS) (113 ± 61.6) conditioned media compared to the control (6mM, 0% FBS media) (5.813 ± 4.279) (n=6, *p<0.05). The MPA showed hyperglycemic culture had effects on SC secreted proteins with large significant differences in proteins: ANGPT1, PECAM-1, and SDF-1 (n=5, *p<0.05). Our flow cytometry and histology data suggests there are exercise induced differences with SC number trending greater in RT than LDC in both db/db (p=0.33) and WT mice (p=.194) (n=3-4 mice/genotype/treatment group).