title: Human C-reactive protein induces endothelial dysfunction in biobreeding diabetic rats.
abstract: OBJECTIVE
  C-reactive protein (CRP) levels in diabetes predict cardiovascular events. Also, human CRP (hCRP) exacerbated the proinflammatory, pro-oxidant and procoagulant states in a spontaneous model of type 1 diabetes mellitus (T1DM), the biobreeding (BB) rat. Since there is a paucity of data examining the role of CRP on endothelial dysfunction in animal models of diabetes, we tested this hypothesis in the diabetic BB rat.
  
  
  METHODS
  Diabetic BB rats (n = 4 per group) were injected with human serum albumin (HSA) or hCRP [hCRP = 20 mg/kg body weight; intraperitoneal (IP)] for three consecutive days. The rats were euthanized on day 4. Biomarkers that were assayed included endothelin-1 (ET-1), soluble intracellular adhesion molecule-1 (sICAM-1), Von Willebrand factor (vWF) and 6-keto prostaglandin F1-alpha (6-keto PGF1-α) in plasma.
  
  
  RESULTS
  hCRP administration resulted in a significant increase in plasma levels. Furthermore, hCRP-treated rats had significantly increased circulating levels of ET-1 (1.12 ± 0.6 pg/mL versus 0.4 ± 0.21 pg/mL), vWF (45 ± 2.4 ng/mL versus 34 ± 7 ng/mL) and sICAM-1 (41 ± 3 ng/mL versus 34 ± 3.4 ng/mL) compared to HSA-treated rats (p < 0.05). There was no significant effect on 6-keto PGF1-α levels.
  
  
  CONCLUSIONS
  Hence, in this preliminary report, we make the novel observation that hCRP induces endothelial dysfunction in a spontaneous model of T1DM, and this could have implications for the vascular complications in diabetics.
authors.affiliation: Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology and Laboratory Medicine, UC Davis Medical Center, Sacramento, CA, USA.
authors.forename: Ishwarlal
authors.initials: I
authors.lastname: Jialal
authors.forename: Harmeet
authors.initials: H
authors.lastname: Kaur
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
authors.forename: Gerred
authors.initials: G
authors.lastname: Smith
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000008:administration & dosage*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000097:blood / Q000503:physiopathology*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D011913:Rats, Inbred BB; D013997:Time Factors
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein
keywords: C-reactive protein; endothelial dysfunction; inflammation; type 1 diabetes mellitus