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.
|Number of pages||8|
|State||Published - Sep 2012|
Bibliographical noteFunding Information:
This work was partially supported in part by grants from the National Institutes of Health (DK55053, HL59791, HL63067; PI: JAB), ADA award # 1-06-RA-09 and Victorian Government's Operational Infrastructure Support Program.
- C-reactive protein
- Microvessel rarefaction
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Cardiology and Cardiovascular Medicine