The finding published in PLoS One suggests that elevated oxidized LDL cholesterol and fructosamine -- a measure of glycated proteins in blood sugar -- are signposts for the development of severe coronary disease, especially in females
Insulin resistance affects tens of millions of Americans and is a big risk factor for heart disease. Yet, some people with the condition never develop heart disease, while some experience moderate coronary blockages. Others, though, get severe atherosclerosis - multiple blockages and deterioration of coronary arteries characterized by thick, hard, plaque-ridden arterial walls. Researchers at the UNC School of Medicine created a first-of-its-kind animal model to pinpoint two biomarkers that are elevated in the most severe form of coronary disease.
The study, published today in the journal PLoS One, suggests two new targets - oxidized LDL cholesterol and glycated proteins (i.e., fructosamine or hemoglobin A1c) - that researchers can further investigate and perhaps target through medications to help people with insulin resistance avoid the worst kind of heart disease.
"If these correlations were also found in insulin resistant humans, then we would want to do everything we could to treat them because they would be at a very high risk of developing severe cardiovascular disease," said Timothy Nichols, MD, professor of medicine and pathology and first author of the PLoS One paper.
Interestingly, Nichols and his colleagues did not set out to pinpoint the two key biomarkers. They wanted to create an insulin resistant animal model that mimicked human heart disease. They chose pigs, which are metabolically similar to humans and have hearts very much like human hearts. By feeding the animals a diet high in fat and salt over the course of a year, all the pigs became insulin resistant. That is, their bodies produced a lot of insulin but their cells did not respond to the hormone as well as normal. All the pigs also developed coronary and aortic atherosclerosis. But only about half of the pigs developed the most severe form of the disease.
When the researchers checked the pigs for high levels of insulin resistance, they found no correlation with the most severe atherosclerosis. This was a surprising and unexpected finding.
David Clemmons, MD, the Sarah Graham Kenan Professor of Medicine, professor of biochemistry and biophysics, and senior author of the PLoS One paper, knew that the scientific literature suggested a correlation between atherosclerosis and glycated proteins - proteins bonded with sugars in blood.
Clemmons and colleagues tested the pigs for high levels of fructosamine and oxidized LDL cholesterol, which are surrogates for high levels of glycated proteins. Sure enough, all the pigs with severe heart disease had elevated levels of fructosamine and oxidized LDL.
"Also, this correlation was more common in females," Clemmons said. Fourteen of the 20 pigs that developed severe atherosclerosis were females. Fourteen of the 17 pigs that did not develop severe atherosclerosis were male. "This surprised me, so I looked in the literature for anything similar."
Clemmons found a study from Finland published in 2005 showing that elevated glycated protein levels were strongly associated with advanced heart disease and increased mortality in women but not in men.
"The underlying causes of this correlation are unknown," Clemmons said. "But now we have a unique animal model that very much mimics what we see in humans. Our model is a good predictor of diet-induced atherosclerosis in females."
A next step could be to study the affected heart tissue to find abnormal biochemical reactions in the cellular pathways involved in glycated proteins and severe coronary disease. This could lead to potential new treatment approaches or tailored dietary interventions.
Clemmons added, "We could also study what's different about these female pigs that make them much more susceptible to severe heart disease, if they have higher levels of glycated proteins."
The National Institutes of Health and the North Carolina Biotechnology Center funded this research.
Timothy Nichols, MD is a physician at the UNC Heart and Vascular Center and director of the Francis Owen Blood Research Laboratory. David Clemmons, MD, is a member of the UNC Diabetes Care Center.
Mark Derewicz | EurekAlert!
New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM
A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
26.04.2017 | Materials Sciences
26.04.2017 | Agricultural and Forestry Science
26.04.2017 | Physics and Astronomy