出版社：American Society for Biochemistry and Molecular Biology
摘要：C-reactive protein (CRP) has been suggested to exert directadverse effects on the vasculature in experimental setups, includingendothelial dysfunction and proinflammatory changes. Here, weassessed the consequences of 1.25 mg/kg highly purified recombinanthuman CRP, administered as an intravenous bolus, in six patientswith familial hypercholesterolemia (FH) and six normocholesterolemicsubjects. Endothelium-dependent and -independent vasoreactivityto serotonin and nitroprusside, respectively, were assessedusing venous occlusion plethysmography before and after CRPinfusion. For biochemical analyses, blood was drawn at differenttime points. At baseline, FH patients showed blunted endothelium-dependentvasodilation (maximum, 89.2 ± 30.0% vs. 117.7 ±13.1% in normolipidemic subjects; P = 0.037). Procoagulant activitywas also higher in FH patients, illustrated by increased prothrombinfragment 1+2 (F1+2) levels (P = 0.030) and plasminogen activatorinhibitor type-1 (PAI-1) activity (P = 0.016). Upon CRP challenge,endothelium-dependent vasodilator capacity further deterioratedin FH patients (P = 0.029), whereas no change in vascular reactivitywas observed in normolipidemic subjects. Additionally, coagulationactivation was augmented in FH patients compared with normolipidemicsubjects (P = 0.009 for F1+2 levels; P = 0.018 and P = 0.003for PAI-1 antigen and activity, respectively). No differencein inflammatory responses was observed between groups. In hypercholesterolemicpatients, CRP aggravates endothelial dysfunction and also evokesaugmented procoagulant responses. These findings suggest thatparticularly in hypercholesterolemia, CRP-lowering strategiesshould be considered in addition to LDL reduction.Supplementary key words inflammation • atherothrombosis • C-reactive protein
