Discovery of new heart failure trigger could change the way cardiovascular drugs are made

July 18, 2012 in Cardiology

Discovery of new heart failure trigger could change the way cardiovascular drugs are made

Enlarge

APJ's yin-yang role in cardiac function: the receptor APJ serves a dual function in heart health, depending on how it’s activated. While APJ enhances heart health upon binding the hormone apelin (green), APJ can also trigger heart enlargement and failure when it senses certain mechanical changes (red). Credit: Sanford-Burnham Medical Research Institute

In their quest to treat cardiovascular disease, researchers and pharmaceutical companies have long been interested in developing new medicines that activate a heart protein called APJ. But researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) and the Stanford University School of Medicine have now uncovered a second, previously unknown, function for APJ—it senses mechanical changes when the heart is in danger and sets the body on a course toward heart failure. This means that activating APJ could actually be harmful in some cases—potentially eye-opening information for some heart drug makers. The study appears July 18 in Nature.

"Just finding a molecule that activates APJ is not enough. What's important to is not if this receptor is 'on' or 'off,' but the way it's activated," said Pilar Ruiz-Lozano, Ph.D., who led the study. Ruiz-Lozano, formerly assistant professor at Sanford-Burnham, is now associate professor of pediatrics in the Stanford University School of Medicine and adjunct faculty member at Sanford-Burnham.

Stretching the heart

APJ is a receptor that sits on the cell surface in many organs, where it senses the external environment. When a hormone called apelin comes along and binds APJ, it sets off a molecular chain reaction that influences a number of cellular functions. Many previous studies have shown that apelin-APJ activity directs beneficial processes such as embryonic heart development, maintenance of normal blood pressure, and new blood vessel formation.

According to Ruiz-Lozano's latest study, however, APJ can also be activated a second, more harmful, way that doesn't involve apelin. In this pathway, APJ senses and responds to mechanical changes in the heart.

To better understand these mechanical changes, let's look at a person with high blood pressure. In this case, the person's heart has to work harder to pump the same amount of blood at the same rate as a healthy person. To meet the increased demand, individual heart muscle cells start making more proteins, making the cells bigger. Eventually, cell membranes stretch and each cell begins to pull away from its neighbor. This leads to an enlarged heart—a condition known as hypertrophy. In pathological (disease) conditions, hypertrophy can lead to heart failure.

APJ and heart failure

The best way to determine the role a plays in a particular cellular process is to see what happens when it's missing. To do this, Ruiz-Lozano's team, including co-first authors Maria Cecilia Scimia, Ph.D. and Cecilia Hurtado, Ph.D., used mice that lack APJ. Under everyday conditions, the APJ-deficient mice appeared perfectly normal. However, unlike their normal counterparts, the mice lacking APJ couldn't sense danger when their hearts enlarged. As a result, mice were actually healthier without APJ—none succumbed to heart failure.

"In other words, without APJ, ignorance is bliss—the heart doesn't sense the danger and so it doesn't activate the hypertrophic pathways that lead to heart failure," Ruiz-Lozano said. "This tells us that, depending on how it's done, activating APJ might make matters worse for disease patients."

Journal reference: Nature search and more info website

Provided by Sanford-Burnham Medical Research Institute search and more info website

5 /5 (2 votes)  

Rank 5 /5 (2 votes)
Related Stories
Relevant PhysicsForums posts

More news stories

Free fatty acids linked to cardiac risk in late adulthood

(HealthDay)—Blood levels of free fatty acids are associated with insulin resistance during young adulthood and cardiovascular risk factors in later adulthood, according to a study published online May 13 ...

Cardiology created May 17, 2013 | popularity not rated yet | comments 0 | with audio podcast

Diagnosing heart attacks: There's an app for that

An experimental, inexpensive iPhone application transmitted diagnostic heart images faster and more reliably than emailing photo images, according to a research study presented at the American Heart Association's Quality ...

Cardiology created May 17, 2013 | popularity not rated yet | comments 0

Study suggests new role for ECMO in treating patients with cardiac arrest and profound shock

Extracorporeal membrane oxygenation (ECMO), a procedure traditionally used during cardiac surgeries and in the ICU that functions as an artificial replacement for a patient's heart and lungs, has also been used to resuscitate ...

Cardiology created May 17, 2013 | popularity not rated yet | comments 0

Stroke patients respond similarly to after-stroke care, despite age difference

Age has little to do with how patients should be treated after suffering a stroke, according to new research from the University of Georgia.

Cardiology created May 17, 2013 | popularity not rated yet | comments 0 | with audio podcast

Depression linked to almost doubled stroke risk in middle-aged women

Depressed middle-aged women have almost double the risk of having a stroke, according to research published in Stroke: Journal of the American Heart Association.

Cardiology created May 16, 2013 | popularity not rated yet | comments 0


Researchers identify a potential new risk for sleep apnea: Asthma

Researchers at the University of Wisconsin have identified a potential new risk factor for obstructive sleep apnea: asthma. Using data from the National Institutes of Health (Heart, Lung, and Blood Institute)-funded Wisconsin ...

Computational tool translates complex data into simplified 2-dimensional images

In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual ...

New theory on genesis of osteoarthritis comes with successful therapy in mice

Scientists at Johns Hopkins have turned their view of osteoarthritis (OA) inside out. Literally. Instead of seeing the painful degenerative disease as a problem primarily of the cartilage that cushions joints, ...

Study finds that sleep apnea and Alzheimer's are linked

A new study looking at sleep-disordered breathing (SDB) and markers for Alzheimer's disease (AD) risk in cerebrospinal fluid (CSF) and neuroimaging adds to the growing body of research linking the two.

'Gap' for HIV vaccine efforts after latest setback

The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.

Ginger compounds may be effective in treating asthma symptoms

Gourmands and foodies everywhere have long recognized ginger as a great way to add a little peppery zing to both sweet and savory dishes; now, a study from researchers at Columbia University shows purified components of the ...