Relation of C-reactive protein to endothelial fibrinolytic function in healthy adults

Increased plasma concentrations of C-reactive protein (CRP) independently predict future atherothrombotic events in healthy asymptomatic adults. CRP may promote atherothrombosis by altering fibrinolytic balance; however, the influence of increased plasma CRP concentrations on endothelial fibrinolysis in healthy adults is unclear. We tested the hypothesis that endothelial release of tissue-type plasminogen activator (t-PA) is impaired in adults with increased plasma CRP concentrations independent of other cardiometabolic risk factors. Fifty-four healthy adults were studied: 24 with CRP <1.0 mg/L (low CRP; 18 men and 6 women, 55 ± 2 years old), 18 with CRP 1.0 to 3.0 mg/L (moderate CRP; 8 men and 10 women, 58 ± 2 years old), and 12 with CRP >3.0 mg/L (high CRP; 7 men and 5 women, 56 ± 2 years old). Net endothelial release of t-PA was determined in vivo in response to intrabrachial infusions of bradykinin (125 to 500 ng/min) and sodium nitroprusside (2.0 to 8.0 μg/min). Capacity of the endothelium to release t-PA was significantly lower (∼30%) in the high (0.32 ± 0.5 to 38.9 ± 6.0 ng · 100 ml tissue ^-1 · min ^-1) and moderate (-0.05 ± 0.4 to 39.3 ± 5.2 ng · 100 ml tissue ^-1 · min ^-1) compared to the low (0.42 ± 0.9 to 61.8 ± 5.2 ng · 100 ml tissue ^-1 · min ^-1) CRP group. There was no significant difference in t-PA release between the high and moderate CRP groups. Plasma CRP concentrations were inversely related to t-PA release (r = -0.38, p <0.05). In conclusion, these results indicate that the capacity of the endothelium to release t-PA is decreased in adults with plasma CRP <1.0 mg/L. Endothelial fibrinolytic dysfunction may underlie the increased atherothrombotic risk associated with increases in plasma CRP concentrations in otherwise healthy adults.