Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UCSD Team Identifies Potential Role of CRP in Development of Atherosclerosis

10.09.2002


Another piece of the complex puzzle of how inflammation is involved in heart attacks and strokes has been discovered by researchers at the University of California, San Diego (UCSD) School of Medicine.


Mi-Kyung Chang, M.D., first author
© UCSD


Joseph Witztum, M.D., and Mi-Kyung Chang, M.D.
© UCSD



Their findings demonstrate that C-reactive protein (CRP) binds to oxidized low density lipoprotein (LDL), implicating the interaction of CRP and oxidized LDL as a potential trigger for the cascade of events leading to atherosclerosis. This form of artery disease is characterized by the buildup of fatty deposits and chronic inflammation along the artery wall, eventually leading to heart attack.

Published in the online edition of Proceedings of the National Academy of Sciences (PNAS) the week of Sept. 9, 2002, the study by the UCSD researchers pinpoints how CRP attaches itself to oxidized LDL, the so-called "bad cholesterol" that accumulates in the artery wall and generates atherosclerotic plaques. LDL is the major cholesterol carrying particles. When they enter the artery wall from the circulation, they are believed to be modified by oxidation. It is this "oxidized LDL" that is thought to be the culprit leading to inflammation and cholesterol accumulation.


"Our study points out that CRP is not merely a marker of future cardiovascular events, as most people believe, but it actually binds to oxidized LDL and apoptotic or dying cells, giving it a potential role in development or modulation of atherosclerosis, as well as in other inflammatory disease," said Mi-Kyung Chang, M.D., an assistant project scientist and the first author of the paper in PNAS.

In the new studies, the UCSD team showed that CRP binds to oxidized LDL through the recognition of phosphocholine, a part of an oxidized molecule on the surface that is exposed when LDL undergoes oxidation.

Noting that there is an accumulation of dead and dying cells (apoptotic cells) in atherosclerotic lesions and that these cells are under increased oxidative stress, the UCSD researchers also determined that CRP binds to these cells in a similar manner as it recognizes oxidized LDL.

CRP is conventionally regarded as a first-line defense of the immune system against invading pathogens and confers protection to humans by removing pathogens. Recently, CRP has been reported as a useful marker for predicting future atherosclerotic cardiovascular events, but the basis for this correlation remains unclear.

Although scientists still do not understand all the steps in the development of atherosclerosis, it is known that oxidized LDL in the artery wall are taken up (engulfed) by macrophages, scavenger cells that have been drawn to the site by oxidized LDL. When they become engorged with the oxidized LDL, the macrophages become "foam cells," the hallmark of atherosclerotic plaques. It is possible that CRP may bind to oxidized LDL and further enhance the uptake into cells.

The paper’s senior author, Joseph Witztum, M.D., professor of medicine, added that cholesterol is still a key player in coronary heart disease. He said that CRP may be working in its "correct role" as part of the immune response to the toxic oxidized LDL and may help promote its clearance.

"If you have low levels of LDL, and thus, low levels of oxidized LDL, then CRP may be of benefit," Witztum said. "However, when there is an overwhelming accumulation of LDL, and thus oxidized LDL, in its attempt to help clear the toxic particle, the CRP may actually make things worse. It may cause more oxidized LDL to be taken up into macrophage scavenger cells, which in turn cause cholesterol accumulation – a sort of ’Trojan horse’."

For the past 20 years, the Witztum lab at UCSD, in collaboration with UCSD professor of medicine Daniel Steinberg, M.D., Ph.D., has pioneered the role of oxidized LDL as a major contributing factor for the development of atherosclerosis. In particular, the Witztum lab has been studying immunological response to oxidized LDL and its impact on development and modulation of atherosclerosis. Recently, the Witztum team found that many mouse antibodies that are specific to oxidized LDL are identical to "T15" type natural antibodies that have been extensively studied for 30 years by immunologists for their recognition of S. pneumoniae, the most common cause of pneumonia. T15 also binds to phosphocholine present on pathogens and provides a protective immune defense against those pathogens.

As both T15 antibody and CRP recognize the same molecule, phosphocholine, Chang reasoned that CRP might bind to oxidized LDL, but not native LDL that does not expose phosphocholine. Indeed, Chang and colleagues showed that CRP does bind to oxidized LDL as well as apoptotic cells through the recognition of phosphocholine. Therefore, CRP is now a novel immune response to oxidized LDL, along with macrophages and T15 antibodies, through the recognition of the same phosphocholine molecule, which is also present on many infectious pathogens.

Studies are now underway to determine whether CRP is protective, or could actually cause harm.

The UCSD research was funded by the National Institutes of Health. In addition to Chang and Witztum, additional authors were Christoph J. Binder, Ph.D., post doctoral fellow, and Michael Torzewski, M.D., visiting scholar, UCSD Department of Medicine.

University of California - San D | EurekAlert!
Further information:
http://health.ucsd.edu/news/

More articles from Health and Medicine:

nachricht A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital

nachricht Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

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...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

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...

Im Focus: Deep inside Galaxy M87

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...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

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...

Im Focus: Microprocessors based on a layer of just three atoms

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

DGIST develops 20 times faster biosensor

24.04.2017 | Physics and Astronomy

Nanoimprinted hyperlens array: Paving the way for practical super-resolution imaging

24.04.2017 | Materials Sciences

Atomic-level motion may drive bacteria's ability to evade immune system defenses

24.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>