Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New pathway discovered at Stanford provides insight into heart disease

13.11.2003


A new signaling pathway appears to play a critical role in the development of heart disease, according to researchers at Stanford University School of Medicine. Now that this marker of cardiac dysfunction, known as the APJ-apelin pathway, has been identified, it could lead to better diagnosis of heart problems, perhaps even allowing doctors to intervene in heart disease by blocking or boosting levels of critical proteins.

"The thing that’s clear is that apelin is increased in heart failure," said Euan Ashley, MD, PhD, a clinical fellow in cardiovascular medicine and one of the lead authors of the study, which is being presented at a Nov. 12 poster session at the annual American Heart Association meeting in Orlando.

"The idea of a blood test to help make a diagnosis of heart disease is very appealing," Ashley said. "But my bigger hope is for therapeutic potential, and given what we know about apelin levels changing a lot during heart failure, either blocking or enhancing this system may provide a treatment for heart failure."



The apelin-APJ signaling pathway’s role in cardiac health was discovered through straightforward techniques combined in such a way that made a previously unnoticed connection apparent. Researchers united Stanford’s long experience with cardiac-assist devices with the ability of microarrays to scan for the activity of thousands of genes at once. In the study, researchers looked at two different heart tissue samples from each patient. One sample came from patients suffering end-stage heart disease before any type of surgical intervention, and the second sample was taken after the same patients’ hearts had recovered with the help of artificial pumps known as left-ventricular assist devices, or LVADs.

The patients in this study relied upon LVADs for up to a year to pump their blood as they waited for an appropriate donor heart to become available for transplant. When the device was implanted, a small section of heart tissue had to be removed, which provided the "before" sample for the study. Once a donor heart arrived, the patient’s old heart became the "after" sample.

"By comparing the two states, the genes we are seeing show the differences between the patients at their worst and when their hearts have had a chance to recover for a bit," said Mary Chen, life science research assistant in cardiovascular medicine and the other lead author of the study. In other words, the things that get worse during heart failure improve with the aid of an LVAD.

Genes that change during the recovery process could provide valuable insight into the progression of heart disease because heart tissue after LVAD use approximates the patient’s healthy heart. The researchers screened matched samples from 11 male patients before and after their heart transplants using microarrays to test for the activity of more than 12,000 genes. Among the genes that changed greatly between the two states was one called BNP, already known to be the first marker of heart disease to date. While this provided some confirmation of their technique, far more intriguing was the discovery of a new pathway.

"Right at the top of our list was a gene that nobody had paid any attention to," said Ashley. "That was our first light bulb." He explained that the gene they found to be most active in the recovering heart was related to angiotensin - shown 20 years ago to be important in heart failure, leading to the class of drugs known as ACE inhibitors. The gene they found produces a receptor called APJ. The protein that combines with this receptor is apelin, which had been shown recently to be perhaps the most potent stimulator of heart contractions ever discovered. Nobody had connected apelin and APJ to cardiac failure until now, the researchers said.

To provide further evidence that apelin played a role in heart disease, the Stanford team detected the protein in human blood. Once they determined what a normal range was, they looked at patients with various stages of heart disease and found that the level of apelin in a person’s blood reflected the condition of their heart determined by standard methods. They further showed that apelin is located in the lining of the blood vessels, but it signals to the receptor APJ in the heart.



Other Stanford researchers who contributed to this presentation are Alicia Deng, life science research assistant in cardiovascular medicine; Philip Tsao, PhD, assistant professor of research in cardiovascular medicine; and Thomas Quertermous, MD, the William G. Irwin Professor in Cardiovascular Medicine. This work was supported by the Donald W. Reynolds Cardiovascular Clinical Research Center at Stanford.

Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children’s Hospital at Stanford. For more information, please visit the Web site of the medical center’s Office of Communication & Public Affairs at http://mednews.stanford.edu.

PRINT MEDIA CONTACT: Mitzi Baker at 650-725-2106 (mitzibaker@stanford.edu)
BROADCAST MEDIA CONTACT: M.A. Malone at 650-723-6912 (mamalone@stanford.edu)

Mitzi Baker | EurekAlert!
Further information:
http://med-www.stanford.edu/MedCenter/MedSchool/

More articles from Health and Medicine:

nachricht Inselspital: Fewer CT scans needed after cerebral bleeding
20.03.2019 | Universitätsspital Bern

nachricht Building blocks for new medications: the University of Graz is seeking a technology partner
19.03.2019 | Karl-Franzens-Universität Graz

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: The taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Solving the efficiency of Gram-negative bacteria

22.03.2019 | Life Sciences

Bacteria bide their time when antibiotics attack

22.03.2019 | Life Sciences

Open source software helps researchers extract key insights from huge sensor datasets

22.03.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>