Disuse and subsequent recovery resistance training affect skeletal muscle angiogenesis-related markers regardless of prior resistance training experience

We recently reported that resistance-trained (T, <i>n</i> = 10) and untrained (UT, <i>n</i> = 11) young adults experience vastus lateralis (VL) muscle atrophy following 2 wk of disuse, and 8 wk of recovery resistance training (RT) promotes VL hypertrophy in both participant cohorts. Skeletal muscle angiogenesis is appreciated for supporting skeletal muscle hypertrophy, but its activity following disuse-induced atrophy in humans is largely unexplored in the context of RT. Thus, we sought to determine whether these outcomes were affected. VL biopsies were obtained at baseline (PRE), immediately after disuse (MID), and after RT (POST). Western blotting was used to assay angiogenesis markers, and immunohistochemistry was performed in 16/21 participants to determine type I and II muscle fiber capillary number. Significant main effects of time (<i>P</i> < 0.05) were observed for protein levels of vascular endothelial growth factor (VEGF) (MID < POST), VEGF receptor-2 (VEGFR2; PRE&MID < POST), thrombospondin1 (TSP-1; PRE < POST), TIMP metallopeptidase inhibitor 1 (TIMP1; MID < POST), phosphorylated/pan endothelial nitric oxide synthase (eNOS) (Ser1177) (POST < PRE), and pan eNOS (PRE < POST). VEGFR2 exhibited a training status × time interaction (<i>P</i> = 0.018), but no differences existed between T and UT at any time point. A significant main effect of time was observed for type II fiber capillary number (PRE < POST), and type II fiber cross-sectional area (fCSA) increased from MID to POST (+25%, <i>P</i> < 0.001) and PRE to POST (+20%, <i>P</i> = 0.019). No significant correlations exist for percentage changes in type II fiber capillary number and type II fCSA from PRE-to-MID (<i>r</i> = 0.020), MID-to-POST (<i>r</i> = 0.392), or PRE-to-POST (<i>r</i> = -0.120) across all participants (<i>P</i> > 0.100). Although disuse and recovery RT affect skeletal muscle angiogenesis-related protein targets, prior training history does not differentially affect these outcomes.<b>NEW & NOTEWORTHY</b> As a follow-up to our original investigation by Michel JM et al. <i>J Appl Physiol (1985)</i> 138: 450-467, 2025, we sought to examine how limb immobilization and recovery resistance training affect molecular outcomes related to angiogenesis in younger adults with or without a prior training history. Regardless of resistance training history, the molecular responses are largely similar between participant cohorts and are suggestive of a reduced (PRE-MID) and increased (MID-POST) angiogenic response, with disuse and subsequent recovery resistance training.