title: Increased myocardial prevalence of C-reactive protein in human coronary heart disease: direct effects on microvessel density and endothelial cell survival.
abstract: BACKGROUND
  Elevated plasma C-reactive protein (CRP) is a biomarker of cardiovascular diseases (CVDs), but its potential roles as a participant of the disease process are not well defined. Although early endothelial cell injury and dysfunction are recognized events in CVD, the initiating events are not well established. Here we investigated the local myocardial CRP levels and cardiac microvessel densities in control and CVD tissue samples. Using in vitro methodologies, we investigated the direct effects of CRP on human endothelial cells.
  
  
  METHODS
  Cardiac specimens were collected at autopsy within 4 h of death and were classified as normal controls or documented evidence of CVD. The regional prevalence of CRP and the cardiac microvessels (<40 μm) were investigated using immunohistochemistry. For in vitro experiments, human umbilical vein endothelial cells were incubated with CRP. Intracellular oxidant levels were assessed using 2',7'-dichlorofluorescein diacetate fluorescence microscopy, and cell survival was concurrently determined. Effects of chemical antioxidants on endothelial cell survival were also tested.
  
  
  RESULTS
  Myocardial CRP levels were elevated in CVD specimens. This was associated with reduced cardiac microvessels, and this rarefaction was inversely correlated to adjacent myocardial CRP prevalence. CRP caused concentration-dependent increases in oxidant production and cell apoptosis.
  
  
  CONCLUSIONS
  These findings provide evidence supporting myocardial CRP as a locally produced inflammatory marker and as a potential participant in endothelial toxicity and microvascular rarefaction.
authors.affiliation: The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton Victoria 3168, Australia. mandar.joshi@monash.edu
authors.forename: Mandar S
authors.initials: MS
authors.lastname: Joshi
authors.forename: Liyue
authors.initials: L
authors.lastname: Tong
authors.forename: Angela C
authors.initials: AC
authors.lastname: Cook
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Schanbacher
authors.forename: Hong
authors.initials: H
authors.lastname: Huang
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Leona W
authors.initials: LW
authors.lastname: Ayers
authors.forename: John Anthony
authors.initials: JA
authors.lastname: Bauer
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003327:Coronary Disease / Q000378:metabolism / Q000473:pathology*; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D055806:Microvessels / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*
chemical_list: D000975:Antioxidants; D002097:C-Reactive Protein