**Development of an Exercise Training Protocol to Investigate Arteriogenesis in a Murine Model of Peripheral Artery Disease**

**Ayko Bresler 1, Johanna Vogel 2, Daniel Niederer 2, Daphne Gray 1, Thomas Schmitz-Rixen 1 and Kerstin Troidl 1,3,\***


Received: 27 July 2019; Accepted: 13 August 2019; Published: 14 August 2019

**Abstract:** Exercise is a treatment option in peripheral artery disease (PAD) patients to improve their clinical trajectory, at least in part induced by collateral growth. The ligation of the femoral artery (FAL) in mice is an established model to induce arteriogenesis. We intended to develop an animal model to stimulate collateral growth in mice through exercise. The training intensity assessment consisted of comparing two di fferent training regimens in C57BL/6 mice, a treadmill implementing forced exercise and a free-to-access voluntary running wheel. The mice in the latter group covered a much greater distance than the former pre- and postoperatively. C57BL/6 mice and hypercholesterolemic ApoE-deficient (ApoE−/−) mice were subjected to FAL and had either access to a running wheel or were kept in motion-restricting cages (control) and hind limb perfusion was measured pre- and postoperatively at various times. Perfusion recovery in C57BL/6 mice was similar between the groups. In contrast, ApoE−/− mice showed significant di fferences between training and control 7 d postoperatively with a significant increase in pericollateral macrophages while the collateral diameter did not di ffer between training and control groups 21 d after surgery. ApoE−/− mice with running wheel training is a suitable model to simulate exercise induced collateral growth in PAD. This experimental set-up may provide a model for investigating molecular training e ffects.

**Keywords:** arteriogenesis; exercise training; mouse model; femoral artery ligation; running wheel; voluntary training; peripheral artery disease
