title: Relation of C-reactive protein to endothelial fibrinolytic function in healthy adults.
abstract: 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.
authors: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, USA.
authors: Brian R
authors: BR
authors: Weil
authors: Jared J
authors: JJ
authors: Greiner
authors: Christopher A
authors: CA
authors: DeSouza
authors: Brian L
authors: BL
authors: Stauffer
mesh_terms: D002097:C-Reactive Protein / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000503:physiopathology; D011379:Prognosis; D012016:Reference Values
chemical_list: D002097:C-Reactive Protein