Protein inhibitor holds promise for heart disease treatment

July 25, 2013, UC Davis

UC Davis scientists have developed a novel cardiovascular agent which, unlike currently available drugs for heart disease, does not target high blood cholesterol or high blood pressure. The experimental agent inhibits C-reactive protein (CRP), a biomarker of risk for heart attacks, strokes and unstable, or uncontrolled, chest pain.

The researchers reported their laboratory animal studies on the experimental agent in an article published online July 22 in the International Journal of Cardiology.

"There is an urgent need to develop inhibitors that specifically block the biological effects of C-reactive protein," said Ishwarlal Jialal, senior author of the article and professor of pathology and laboratory medicine at UC Davis.

Jialal said that his lab's development of the CRP inhibitor reflects the major shift that has occurred in how physicians and scientists view . The change is based on recent studies that have shown that the body's inflammatory response is pivotal to all phases of cardiovascular disease, from the development of , or plaques, in blood vessels to the onset of heart attacks and strokes, said Jialal, who directs UC Davis Medical Center's Laboratory of Atherosclerosis and Metabolic Research and holds the Robert E. Stowell Endowed Chair in Experimental Pathology.

"Numerous studies have shown that high levels of CRP result in a poorer prognosis in patients with heart attack and ," he said. Unstable angina is unpredictable, frequent chest pain.

Research also has revealed that individuals whose blood CRP levels are high but whose blood cholesterol and blood pressure are normal are at risk for suffering a , stroke or sudden death from cardiovascular disease, said Jialal.

As an example, Jialal cited a major clinical trial of that found the significantly reduced heart attacks, strokes, chest pains and other cardiovascular disorders in individuals with high CRP blood levels, but no other risk factors for cardiovascular disease.

An estimated 15 to 20 percent of heart attacks and strokes occur in patients without traditional cardiovascular risk factors such as high blood pressure and blood cholesterol, obesity, lack of regular exercise and cigarette smoking.

Jialal's lab synthesized the CRP inhibitor, a peptide, which is a small protein molecule, by using the one-bead-one-compound combinatorial library ( developed by study co-author Kit Lam, chair of the UC Davis Department of Biochemistry and Molecular Medicine and professor of hematology and oncology.

In laboratory cultures of human cells, the inhibitor—named CRP-i2—reduced CRP levels. These findings were reported in early 2013 in the journal Metabolic Syndrome and Related Disorders.

For the current study, Jialal's group injected the inhibitor CRP-i2 in one group of laboratory rats and compared the effects with a second group of lab rats that was not treated with the inhibitor. CRP from human cells was then administered to the animals because rodents do not normally produce the protein. Previous research by scientists in the United Kingdom found that administering human CRP to rodents increased tissue damage from heart attacks or strokes in these animals.

Jialal and his colleagues found that CRP-i2 blunts the pro-inflammatory effects of CRP and significantly reduced biomarkers of inflammation, including nuclear factor kappaB, which he described as the master switch of inflammation. In addition, the inhibitor did not harm the animals.

Before CRP-i2 can be evaluated in human volunteers, Jialal and colleagues will conduct a series of studies over the next five years to evaluate the long-term effects of the agent on the pathobiology of the endothelial cells lining the blood vessels of rat models and on the extent of tissue damage caused by inducing heart attacks in the animals.

The agent developed by Jialal and his colleagues is the third known inhibitor of CRP under development as a potential treatment for cardiovascular disease.

CRP, which is normally present in trace levels in the , is produced by the immune system to clear dead and disintegrating cells. According to research at several labs, inflammation plays a role in Crohn's disease, diabetes, rheumatoid arthritis as well as heart disease. Physicians can measure CRP to determine the general level of inflammation in an individual's body.

The title of journal paper is "A Novel Peptide Inhibitor Attenuates C-Reactive Protein's Pro-Inflammatory Effects in-vivo."

Explore further: Self-monitoring of blood glucose protocol cuts hs-CRP

Related Stories

Self-monitoring of blood glucose protocol cuts hs-CRP

March 7, 2013
(HealthDay)—Among patients with poorly controlled type 2 diabetes, a structured self-monitoring of blood glucose (SMBG) protocol correlates with reductions in the level of high-sensitivity C-reactive protein (hs-CRP), according ...

People with depression may not reap full benefits of healthy behaviors

March 26, 2013
Depression may inhibit the anti-inflammatory effects typically associated with physical activity and light-to-moderate alcohol consumption, according to researchers at Duke Medicine.

Study deflates notion that pear-shaped bodies more healthy than apples

January 10, 2013
People who are "apple-shaped"—with fat more concentrated around the abdomen—have long been considered more at risk for conditions such as heart disease and diabetes than those who are "pear-shaped" and carry weight more ...

Elevated levels of C-reactive protein appear associated with psychological distress, depression

December 24, 2012
Elevated levels of C-reactive protein, a marker of inflammatory disease, appear to be associated with increased risk of psychological distress and depression in the general population of adults in Denmark, according to a ...

Inflammation in depression: Chicken or egg?

January 5, 2012
An important ongoing debate in the field of psychiatry is whether inflammation in the body is a consequence of or contributor to major depression. A new study in Biological Psychiatry has attempted to resolve the issue.

Biomarker trio predicts near-term heart risk

May 21, 2013
(Medical Xpress)—Cardiologists have identified a trio of biomarkers that may predict which patients with heart disease have a high risk of heart attack or death in the next two years.

Recommended for you

Study of nearly 300,000 people challenges the 'obesity paradox'

March 15, 2018
The idea that it might be possible to be overweight or obese but not at increased risk of heart disease, otherwise known as the "obesity paradox", has been challenged by a study of nearly 300,000 people published in in the ...

Mending broken hearts with cardiomyocyte molds

March 13, 2018
2.5 billion. That's approximately the number of times the human heart beats in 70 years. And sometimes during the course of its unrelenting contractions and relaxations, the heart muscle can no longer bear the strain.

Common infections a bigger heart disease and stroke risk than obesity

March 13, 2018
A major study into the impact of common infections leading to hospitalisation has found they may substantially increase the risk of heart attacks, strokes and in the longer term, death.

Aspirin prevents venous thromboembolism following major orthopedic surgeries, study finds

March 13, 2018
A multicentre, double-blind, randomized, controlled clinical trial of patients who underwent total hip or knee replacement surgery showed that aspirin was as effective as rivaroxaban, the standard anti-coagulation medication, ...

Barbershop-based healthcare study successfully lowers high blood pressure in African-American men

March 12, 2018
African-American men successfully lowered their high blood pressure to healthy levels when aided by a pharmacist and their local barber, according to a new study from the Smidt Heart Institute.

One in 10 stroke survivors need more help with taking medication, study finds

March 12, 2018
Over a half of stroke patients require a degree of help with taking medicine and a sizeable minority say they do not receive as much assistance as they need, according a study published today in the journal BMJ Open.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.