Collaboration to use proteomics to unravel mysteries of heart disease

September 03, 2002

DURHAM, N.C. -- Researchers from Duke University Medical Center; GeneProt, Inc., Geneva, Switzerland; and Novartis Pharma AG, Basel, Switzerland have launched a collaboration to identify how the proteins produced by heart disease patients differ from those of healthy people. Their research, which uses an industrial-scale approach to protein analysis and unusually large volumes of blood, could yield information that leads to new drugs or other treatments for coronary artery disease.

The researchers will compare blood samples from heart disease patients and normal people to detect subtle differences in the proteomes of the two groups. The proteome comprises the total number of proteins in an organism, much as a genome comprises its genes.

"This study is a new approach to unraveling the mysteries of the world's No. 1 health problem," said Duke's Chris Granger, a cardiologist at the Duke Clinical Research Institute and lead Duke investigator for the study.

"Although the sequencing of the human genome was heralded as one of science's greatest accomplishments, studies such as this one are essential for determining how the code of life produces the specific proteins that play a role in heart disease," Granger continued.

"This important project links the sophisticated capabilities of GeneProt in proteomic technologies, bioinformatics and protein synthesis to the exquisitely detailed patient phenotypes provided by Duke's unique Databank for Cardiovascular Diseases," said Sandy Williams, M.D., dean of the Duke University School of Medicine and vice chancellor for health affairs at Duke University Medical Center. "I believe this collaboration among Novartis, GeneProt and Duke University, under the leadership of Chris Granger, is a model for academic/industry relationships that will benefit our patients in the coming decade".

To assemble ideal comparison groups with and without coronary artery disease, the research team searched through the tens of thousands of patients entered in Duke's Databank for Cardiovascular Disease, -- the world's largest and longest-running cardiac catheterization-based database -- to select 241 patients who fulfilled specific criteria,. After matching such characteristics as gender, age and ethnicity, they narrowed the group further to 53 individuals, who matched closely with 53 healthy individuals. Then they collected blood from all of the participants and ended up with a total of six liters for each group.

"It is necessary to use large volumes in order to have sufficient quantities of those proteins present at very low concentration -- this involves pooling, which also serves to dilute normal differences with occur between individuals unrelated to the disease process," said Keith Rose, Ph.D., chief scientific officer for GeneProt.

GeneProt has completed its analysis of the smaller proteins and is now analyzing the larger proteins in the samples. Proteins that are present in one sample but not the other, or are present in widely differing amounts, are likely to be associated with the disease process and could be promising candidates for further investigation, according to Granger.

"This is the first time that in-depth proteomic analysis has been tackled on the scale of many liters of plasma, which is greater than 1,000 times more than is usually used," Rose said. "This allows identification of proteins in low concentration that may be novel and important factors in causing disease."

GeneProt then synthesizes the smaller interesting proteins, and Novartis will test them in further studies.

"We analyzed more than 25,000 fractions in our analysis of the small proteins and have delivered Novartis several releases of the protein database," Rose said. "Some interesting new proteins have already been synthesized, which validates our vision of an industrial-scale proteomics approach."

Granger has no financial interest in either GeneProt or Novartis.
-end-


Duke University Medical Center

Related Heart Disease Articles from Brightsurf:

Cellular pathway of genetic heart disease similar to neurodegenerative disease
Research on a genetic heart disease has uncovered a new and unexpected mechanism for heart failure.

Mechanism linking gum disease to heart disease, other inflammatory conditions discovered
The link between periodontal (gum) disease and other inflammatory conditions such as heart disease and diabetes has long been established, but the mechanism behind that association has, until now, remained a mystery.

New 'atlas' of human heart cells first step toward precision treatments for heart disease
Scientists have for the first time documented all of the different cell types and genes expressed in the healthy human heart, in research published in the journal Nature.

With a heavy heart: How men and women develop heart disease differently
A new study by researchers from McGill University has uncovered that minerals causing aortic heart valve blockage in men and women are different, a discovery that could change how heart disease is diagnosed and treated.

Heart-healthy diets are naturally low in dietary cholesterol and can help to reduce the risk of heart disease and stroke
Eating a heart-healthy dietary pattern rich in vegetables, fruits, whole grains, low-fat dairy products, poultry, fish, legumes, vegetable oils and nuts, which is also limits salt, red and processed meats, refined-carbohydrates and added sugars, is relatively low in dietary cholesterol and supports healthy levels of artery-clogging LDL cholesterol.

Pacemakers can improve heart function in patients with chemotherapy-induced heart disease
Research has shown that treating chemotherapy-induced cardiomyopathy with commercially available cardiac resynchronization therapy (CRT) delivered through a surgically implanted defibrillator or pacemaker can significantly improve patient outcomes.

Arsenic in drinking water may change heart structure raising risk of heart disease
Drinking water that is contaminated with arsenic may lead to thickening of the heart's main pumping chamber in young adults, according to a new study by researchers at Columbia University Mailman School of Public Health.

New health calculator can help predict heart disease risk, estimate heart age
A new online health calculator can help people determine their risk of heart disease, as well as their heart age, accounting for sociodemographic factors such as ethnicity, sense of belonging and education, as well as health status and lifestyle behaviors.

Wide variation in rate of death between VA hospitals for patients with heart disease, heart failure
Death rates for veterans with ischemic heart disease and chronic heart failure varied widely across the Veterans Affairs (VA) health care system from 2010 to 2014, which could suggest differences in the quality of cardiovascular health care provided by VA medical centers.

Heart failure: The Alzheimer's disease of the heart?
Similar to how protein clumps build up in the brain in people with some neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, protein clumps appear to accumulate in the diseased hearts of mice and people with heart failure, according to a team led by Johns Hopkins University researchers.

Read More: Heart Disease News and Heart Disease Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.