Abstract Th0079: 24-Dehydrocholesterol Reductase Plays a Significant Role in Inflammation During Peripheral Arterial Disease

Objective: Monocytes play a central role during neovascularization. Our recent data showed that ischemia training modifies bone marrow-derived monocytes (BM-Mono), leading to arteriogenesis after limb ischemia. We demonstrated that 24-dehydrocholesterol reductase (Dhcr24), an essential enzyme in the cholesterol pathway, plays an exciting role in the monocytes during limb ischemia. Methods/Results: BM-Mono from mice exposed to ischemia training or sham were used as donors during adoptive transfer, where recipients were subjected to limb ischemia. Recipients with 24h ischemia BM-Mono had greater perfusion and arteriogenesis than recipients with Sham BM-Mono. Then, we showed that these BM-Mono had downregulation of Dhcr24 and consequent activation of the desmosterol pathway (LXRs and ABCA1). The adoptive transfer using Dhcr24 KO mice as BM-Mono donors for WT mice subjected to limb ischemia showed that recipients had greater limb perfusion. We generated Dhcr24 gain-and-loss of function transgenic mice using myeloid LisM promoter and showed upregulation and downregulation of Dhcr24 gene expression in the monocytes. Currently, we are investigating whether those mice have altered blood flow recovery and arteriogenesis after hindlim limb ischemia surgery. Conclusion: Dhcr24 plays a crucial role in arteriogenesis during limb ischemia and could be a potential target for future therapeutic approaches in peripheral arterial diseases and critical limb ischemia.