Abstract 2030: Endothelial Deletion Of Bag3 Does Not Impair Ischemic Limb Recovery In A Murine Model Of Peripheral Artery Disease

Background: Peripheral artery disease (PAD) is a highly prevalent vascular occlusive disease which mostly affects the lower limb. Emerging studies proved the critical functions of endothelial cells in arteriogenesis and ischemic limb blood flow recovery. However, very few targets with endothelial cell exclusivity have been identified. Here, we explored the role of endothelial BCL-2 associated athanogene 3 (Bag3) in ischemic limb recovery. Hypothesis: We hypothesized that the loss of endothelial specific BAG3 would attenuate blood flow and muscle recovery following HLI. Methods: Hind limb ischemia (HLI) was induced in Bag3 Cdh5(PAC)-CreERT2 male and female mice after tamoxifen (2mg/day x 5 days) or vehicle treatment ( n ≥12/group). Limb blood flow was measured by laser Doppler perfusion imaging (LDPI) and isometric muscle force production, vascular density and muscle morphology were assessed after HLI. Results: LDPI analysis revealed no differences in the blood flow between groups at HLI d7 ( n=9 ; day 7, 21.86% ischemic/non-ischemic ± 3.80% vs 18.05% ± 1.96% SEM; p=0.05). There was no deficit in isometric force recovery of the EDL ( n ≥12; 57.76 ± 15.92 vs 83.05 ± 27.12 SEM; p =0.05) in KO animals at HLI d7. Similar rates of CD31+ vessel disorganization was observed in both groups at HLI d7, ( n =7; 4626.0 um 2 CD31+ area ± 869 vs 4870.9 ± 1056 SEM) consistent with recovering ischemic tissue. There were also no differences in blood flow recovery assessed by LDPI at HLI d28 ( n =7; 50.74% ischemic/non-ischemic ± 7.4% vs 59.17 ± 8.21; n=9). Conclusions: Endothelial cell specific Bag3 knockout did not impair vascular morphology or perfusion recovery at baseline or following HLI in a murine model of peripheral artery disease. No differences in muscle morphology or contractile function at baseline or after HLI at either timepoint were observed. In summary, we reveal an unexpectedly minor role of endothelial cell BAG3 in tissue recovery following ischemic injury.