UC Davis Study Identifies C-reactive Protein As Cause Of Blood Clot Formation

The study demonstrates that CRP causes cells in the arteries, known as human aortic endothelial cells, to produce higher levels of an enzyme that inhibits the breakdown of clots. The enzyme, plasminogen activator inhibitor-1 (PAI-1) is also a strong risk marker for heart disease, especially in diabetics. The study used a variety of techniques to convincingly show how CRP activates PAI-1 in aortic cells, causing lesions in the arteries that ultimately lead to formation of plaque and blood clots.

The study underscores the need to use CRP screening to more accurately assess at-risk populations, according to Jialal, who is the Robert E. Stowell Endowed Chair in Experimental Pathology.

"Based on these findings, if a patient has normal cholesterol but high levels of CRP, an aggressive course of treatment is recommended to help the patient reduce the risk of heart attack, stroke and other heart diseases," said Jialal. "By relying on cholesterol alone, a physician could significantly underestimate a patient's risk level."

High CRP levels can occur in otherwise healthy individuals, according to the study. Patients with high levels of CRP can reduce risk by losing weight, exercising on a regular basis, stopping cigarette smoking, or taking statin drugs, Jialal added.

The study also closely links CRP and PAI-1 to diabetes and metabolic syndrome, a disorder characterized by a disproportionate amount of abdominal fat, elevated blood pressure, blood sugar and triglycerides and low levels of HDL, the "good" kind of cholesterol.

"In another important discovery, this study shows that in the presence of high blood-glucose levels, CRP is especially active in the stimulation of PAI-1. As a result, the effect of CRP is especially acute for patients with diabetes and metabolic syndrome," said Sridevi Devaraj, a co-investigator and assistant professor of pathology at UC Davis. "Given the current pandemic of obesity which increases one's risk of diabetes, the study's insights about the active role of CRP and PAI-1 in heart disease are especially valuable."

The new study adds to the findings of another landmark study on CRP by Jialal's team at UC Davis that showed CRP actually damages the blood vessel wall by blocking a critical "protector" protein and inhibiting nitric oxide.

"Interestingly, the new study indicates that activation of PAI-1 was unrelated to the nitric oxide inhibition identified in the earlier study," said Jialal. "This indicates that CRP has multiple, independent effects that cause heart disease."

Dan Yan Xu, a physician and postgraduate researcher in the pathology department at UC Davis, also contributed to the study.

This study was supported by grants from the National Institutes of Health, the Juvenile Diabetes Foundation and American Diabetes Association.