Exercise - induced differential changes in gene expression among arterioles of skeletal

47 Using next generation, transcriptome-wide, RNA sequencing (RNA-Seq) technology we 48 assessed the effects of exercise training on transcriptional profiles in skeletal muscle arterioles 49 isolated from the soleus and gastrocnemius muscles of Otsuka Long Evans Tokushima Fatty 50 (OLETF) rats that underwent an endurance exercise training program (EX; n=13), interval sprint 51 training program (SPRINT; n=14), or remained sedentary (Sed; n=12). We hypothesized that the 52 greatest effects of exercise would be in the gastrocnemius arterioles. Results show that EX 53 caused the largest number of changes in gene expression in the soleus and white gastrocnemius 54 2a arterioles with little to no changes in the feed arteries. In contrast, SPRINT caused substantial 55 changes in gene expression in the feed arteries. IPA canonical pathway analysis revealed 18 56 pathways with significant changes in gene expression when analyzed across vessels and revealed 57 that EX induces increased expression of the following genes in all arterioles examined: Shc1, 58 desert hedgehog protein (Dhh), adenylate cyclase 4 (Adcy4), G protein binding protein, alpha 59 (Gnat1), and Bcl2l1 and decreased expression of ubiquitin D (Ubd) and cAMP response element 60 modulator (Crem). EX increased expression of endothelin converting enzyme (Ece1), Hsp90b, 61 Fkbp5, and Cdcl4b in 4 of 5 arterioles. SPRINT had effects on expression of Crem, Dhh, Bcl2l1 62 and Ubd that were similar to EX. SPRINT also increased expression of Nfkbia, Hspa5, Tubb 2a 63 and Tubb 2b, and Fkbp5 in all 5 arterioles and increased expression of Gnat1 in all but the soleus 64 second order arterioles. Many contractile and/or structural protein genes were increased by 65 SPRINT in the gastrocnemius feed artery but the same genes exhibited decreased expression in 66 red gastrocnemius arterioles. We conclude that training-induced changes in arteriolar gene 67 expression patterns differ by muscle fiber type composition and along the arteriolar tree. 68 by 10.0.33.6 on M arch 0, 2017 http://jaysiology.org/ D ow nladed fom