Abstract: AIM To study the association between coronary slow flow (CSF) phenomenon and C1q tumor necrosis factor-related protein 6 (CTRP6), and to explore the potential molecular mechanism of CTRP6 impact on CSF. METHODS Each coronary artery blood flow TIMI frame was calculated using corrected TIMI frame count method (cTFC) in CSF group (n=42) and normal control group (n=45), and c1q tumor necrosis factor-related protein 6 in serum was determined using biochemical methods. Then, six CSF patients were randomly selected to phlebotomize peripheral blood, which was used to isolate and culture endothelial progenitor cells (EPCs). EPCs were transfected with pcDNA-CTRP6 overexpression vector. After 3 days, cell proliferation was detected using EdU method and the number of the cells was counted by an automated cell instrument. Finally, the secretion levels of CSF-related factors matrix metalloproteinase 2 (MMP-2) and endothelin-1 (ET-1) were examined and compared. RESULTS CTRP6 levels in CSF group were significantly lower than in control group ［(1.2±0.5) vs.( 2.7±1.0) mg/L, P=0.002］. Logistic regression analysis showed that serum CTRP6 and cTFC content in CSF patients were negatively correlated (β=-1.76), and CTRP6 was a protective factor for CSF (OR=0.395). Moreover, CTRP6 overexpression resulted in a significant increase of EPC number (P<0.05). The secretion levels of MMP-2 were negatively correlated with CSF and were significantly upregulated (P<0.01). Levels of ET-1 positively correlated with CSF were significantly downregulated (P<0.05). CONCLUSION Serum CTRP6 level is lower and is negatively correlated with cTFC content in CSF patients. Serum CTRP6 is a protective factor for CSF and promotes MMP-2 and reduces ET-1 secretion.