The Relationship Between Coronary Artery Shear Stress and Endothelial Progenitor Cells Number and Function

Background: Endothelial progenitor cells (EPCs) are implicated in cardiovascular repair and regeneration. Although previous studies have demonstrated that shear stress leads to upregulation of EPCs in vitro, its effect on EPCs in vivo have never been assessed. We investigated the relationship between coronary artery shear stress and EPC numbers and function. Methods: Consecutive patients (n = 19) undergoing coronary angiography with isolated left anterior descending (LAD) artery disease were recruited. Blood samples were obtained from the peripheral vein (PV), aortic root (AR) and coronary sinus (CS), and EPC counts and angiogenic functional assays were performed. Vessel wall shear stress at the site of LAD lesion was calculated using computational fluid dynamics. Results: Increased shear stress was associated with a higher ratio of CS to AR late Outgrowth Endothelial Cells (OEC) levels (r = 0.602, p = 0.023, n = 14). Higher shear stress levels were also significantly associated with increased OEC migration and proliferation levels in the CS samples versus PV samples (r = 0.574, p = 0.025, n = 15 and r = 0.55, p = 0.044, n = 14, respectively). No such relationship was seen with early EPCs. In addition, shear stress also directly correlated with increased levels of Hepatocyte Growth Factor (HGF) in the CS compared with PV blood (r = 0.534, p = 0.027, n = 17). Conclusion: Our results suggest increased recruitment and activation of OECs within the coronary vasculature in response to greater atherosclerotic vessel wall shear stress, consistent with the proposed role of these cells in coronary vascular repair and regeneration.