Satellite cells (SC) are muscle stem cells important for muscle regeneration. We hypothesized that cigarette smoke (CS) exposure would decrease myofiber associated SCs, in part due to inhibited VEGF expression. SC number per myofiber was measured in wild type (WT), skeletal muscle VEGF gene‐deleted (skmVEGF−/−) and CS exposed mice. Growth of SC colonies in vitro was monitored in myofibers +/− CS extract (CSE) and/or VEGF−/−.MethodsHSA‐Cre‐ ERT2 × VEGFLoxP mice were exposed daily to whole body CS for 4 wks or tamoxifen‐induced skmVEGF−/−. Nes‐GFP+/Pax7+ cells per isolated soleus myofiber were identified by confocal microscopy. Additional fibers were cultured for 4 days in the presence of tamoxifen +/− 2.5% CSE.ResultsGastrocnemius VEGF levels were decreased to the same extent in skmVEGF−/− and smoke exposed mice (17.1 ± 3.9 WT, 5.2 ± 2 skmVEGF−/−, 4.2 ± 1.3 CS, p<0.01). Pax7+/Nes+ cells per soleus fiber were lowest in CS exposed mice but also reduced in the skmVEGF−/− group compared to WT (12 ± 2.2 WT, 7.2 ± 3.3 skmVEGF−/−, 3.5 ± 1.7 CS, p<0.01). Cultured soleus fibers treated with CSE formed long extensions of aggregated SC colonies. In vitro VEGF gene deletion resulted in smaller SC colonies compared to WT mice cultured under control and CSE conditions.ConclusionsCS exposure leads to the loss of SC that may result from inhibited VEGF expression and incorporation into mature myofibers.NIH/NHLBI HL091830‐01A1