Ankrd23 is a member of a conserved family of genes containing four Ankyrin repeats and a binding site for the N2A region of titin1, 2. Ankrd23 is a member of this family of genes and a novel protein discovered in muscle and adipose tissue of diabetic mice and Obese Zucker rats3. Ankrd1, in cardiac muscle 4 and Ankrd2, in skeletal muscle are well known as muscle stretch proteins that are induced under stress conditions and have gene expression regulatory functions1, 5. Ankrd1 and Ankrd2 appear to serve as both nuclear transcriptional regulators, forming molecular links between myofibrillar stretch-induced signaling and muscle gene expression, and as structural proteins along with titin and contractile proteins. The purpose of the study described here-in was to test the hypothesis that Ankrd23 is a muscle stretch sensing transcriptional regulator in vascular smooth muscle, similar to Ankrd 1 and 2 of striated muscle, in that it participates in vascular remodeling through control of vascular gene expression. Using RNA sequence analysis of skeletal muscle arterioles we examined the effects of exercise training (EX) on expression of genes coding for proteins that are pro-angiogenic and/or involved in vascular remodeling, including Ankrd23.6 We found that EX caused a 19 fold increase in Ankrd23 mRNA expression in gastrocnemius feed artery (GFA) and a 2.4 fold increase in white gastrocnemius 2A arterioles. Results also indicate that Ankrd23 mRNA levels increase with increasing branch order in the gastrocnemius arteriolar tree. To test the hypothesis that Ankrd23 is a muscle stretch sensing transcriptional regulator in vascular smooth muscle that participates in control of vascular gene expression, we measured Ankrd23 mRNA in cannulated GFA exposed to 90 and 180 cm H2O intraluminal pressure for 4 hrs. Doubling intraluminal pressure caused a 14- fold increase in Ankrd23 mRNA. When we compared the ability of wild type (WT) and Ankrd23-/- mice to form collateral arteries following femoral artery occlusion; we found very limited collateralization was present in the Ankrd23-/- mice (angioscore WT = 0.18 + 0.03; Ankrd23-/- = 0.04 + 0.01). Also, femoral occluded Ankrd23-/- mice exhibited less contraction induced hyperemia in the soleus and gastrocnemius muscles than in WT. These results are consistent with our hypothesis that Ankrd23 plays an important role in mechanically-induced vascular remodeling of the arterial tree.