Abstract 5584: Extra Domain A of Fibronectin (EDA) is Critically Involved in Collateral Artery Growth
Background Shear stress induced arterial remodeling leading to collateral artery formation (arteriogenesis) is an important protective mechanism in cardiovascular disease, redirecting blood flow around arterial stenoses. Toll Like Receptors (TLRs), part of the innate immune system, play an important role in arterial remodeling, indicating the presence of a yet unknown endogenous ligand responsible for TLR mediated arteriogenesis.
Methods & Results RT-PCR for endogenous TLR ligands was performed in mouse hind limb tissue after femoral artery occlusion (n=10). Hsp60 and EDA, candidate endogenous TLR-4 ligands, were significantly upregulated compared to sham operated hind limbs (EDA: occlusion 0.88±0.77 versus sham 0.0096±0.012 pg plasmid; HSP60: occlusion 0.0050±0.0049 versus sham 0.0026±0.0021 pg plasmid). To address the functional role of the increased EDA expression, EDA −/− (n=22) and corresponding wild type mice (BALB/C, n=22) were subjected to unilateral femoral artery ligation and contra lateral sham operation. Maximum hind limb perfusion restoration was assessed using fluorescent microspheres 7 days after surgery under maximal vasodilation. Perfusion restoration was significantly decreased in EDA −/− mice compared to wild type mice (EDA 22±2.6% vs. BALB/C 31±1.8% of sham operated hind limb perfusion, p=0.011), supporting a critical role of EDA during collateral artery growth.
Conclusion We demonstrate that the Extra Domain A of fibronectin may be the endogenous TLR ligand critically involved in collateral development. Its expression is enhanced during collateral development while its depletion in mice attenuates perfusion restoration after acute arterial occlusion.