title: C-reactive protein induces release of both endothelial microparticles and circulating endothelial cells in vitro and in vivo: further evidence of endothelial dysfunction.
abstract: BACKGROUND
  Inflammation is pivotal in atherosclerosis. A key early event in atherosclerosis is endothelial dysfunction. C-reactive protein (CRP), the prototypic marker of inflammation in humans, is a risk marker for cardiovascular disease, and there is mounting evidence to support its role in atherothrombosis. CRP has been shown to promote endothelial dysfunction both in vitro and in vivo. Emerging biomarkers of endothelial dysfunction include circulating endothelial cells (CECs) and endothelial microparticles (EMPs). However, there is a paucity of data examining the effect of CRP on CEC and EMP production in vitro and in vivo.
  
  
  METHODS
  In this report, we treated human aortic endothelial cells (HAECs) with increasing concentrations of CRP (0-50 μg/mL) or boiled CRP. We counted CECs and EMPs by flow cytometry.
  
  
  RESULTS
  Although CRP treatment resulted in a significant increase in release of both CECs and EMPs, boiled CRP failed to have an effect. Pretreatment of HAECs with sepiapterin or diethylenetriamine NONOate, both of which preserve nitric oxide (NO), resulted in attenuation of CRP's effects on CECs and EMPs. CD32 and CD64 blocking antibodies but not CD16 antibody or lectin-like oxidized LDL receptor 1 small interfering RNA (LOX-1 siRNA) prevented CRP-induced production of CECs and EMPs. Furthermore, delivery of human CRP to Wistar rats compared with human serum albumin resulted in significantly increased CECs and EMPs, corroborating the in vitro findings.
  
  
  CONCLUSIONS
  We provide novel data that CRP, via NO deficiency, promotes endothelial dysfunction by inducing release of CECs and EMPs, which are biomarkers of endothelial dysfunction.
authors: Laboratory for Atherosclerosis and Metabolic Research, University of California-Davis Medical Center, Sacramento, CA, USA.
authors: Sridevi
authors: S
authors: Devaraj
authors: Pappanaicken R
authors: PR
authors: Kumaresan
authors: Ishwarlal
authors: I
authors: Jialal
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D002097:C-Reactive Protein / Q000494:pharmacology / Q000502:physiology*; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000648:ultrastructure*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D009603:Nitroso Compounds / Q000494:pharmacology; D011622:Pterins / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017452:Receptors, IgG / Q000037:antagonists & inhibitors; D051127:Scavenger Receptors, Class E / Q000235:genetics
chemical_list: D000906:Antibodies; D009603:Nitroso Compounds; D011622:Pterins; D034741:RNA, Small Interfering; D017452:Receptors, IgG; D051127:Scavenger Receptors, Class E; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D002097:C-Reactive Protein; C016727:sepiapterin