C-reactive protein (CRP) is a hallmark of inflammation and tissue damage, as in arthritis or infection. It is also widely touted as a marker for cardiovascular disease, with doctors using patient CRP levels to improve risk assessment. However, whether CRP is merely a risk marker or is actually a contributing factor of cardiovascular disease has remained controversial.
To address these issues, Dr. Jianglin Fan's group examined the role of CRP in two rabbit models of atherosclerosis: high cholesterol diet or LDL receptor deficiency. Rabbits represent highly suitable models as they quickly form atherosclerotic plaques in response to high serum cholesterol, and rabbit CRP shares 70% homology with human CRP.
As expected, hypercholesterolemic rabbits developed atherosclerotic plaques. Upon further examination, serum CRP levels were found to positively correlate with plaque size. CRP was found in plaques of various stages, including early and advanced lesions, but it did not appear to associate with macrophages, as had been suggested. Similar results were seen in human aortic lesions.
To determine where CRP protein was being produced, CRP mRNA levels were measured by Northern blot and real-time RT-PCR. CRP mRNA was only detected in liver obtained from atherosclerotic rabbits but was undetectable in vascular cells or macrophages. Again, results were confirmed in human specimens: insignificant mRNA levels found in atherosclerotic aorta compared to high levels in liver. Finally, in vitro analysis revealed that hepatocytes, but not macrophage
Contact: Audra Cox
American Journal of Pathology