Featured Research

from universities, journals, and other organizations

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

Date:
July 18, 2012
Source:
Sanford-Burnham Medical Research Institute
Summary:
In their quest to treat cardiovascular disease, researchers have been interested in developing new medicines that activate a protein called APJ. Medical researchers have now uncovered another function for APJ -- it senses mechanical changes that set the body on a course toward heart failure. This means activating APJ could be harmful in some cases -- potentially eye-opening information for some drug makers.

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.

Related Articles


The study appears July 18 in Nature.

"Just finding a molecule that activates APJ is not enough. What's important to heart failure 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 protein 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 heart disease patients."


Story Source:

The above story is based on materials provided by Sanford-Burnham Medical Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Maria Cecilia Scimia, Cecilia Hurtado, Saugata Ray, Scott Metzler, Ke Wei, Jianming Wang, Chris E. Woods, Nicole H. Purcell, Daniele Catalucci, Takashi Akasaka, Orlando F. Bueno, George P. Vlasuk, Perla Kaliman, Rolf Bodmer, Layton H. Smith, Euan Ashley, Mark Mercola, Joan Heller Brown, Pilar Ruiz-Lozano. APJ acts as a dual receptor in cardiac hypertrophy. Nature, 2012; DOI: 10.1038/nature11263

Cite This Page:

Sanford-Burnham Medical Research Institute. "Discovery of new heart failure trigger could change the way cardiovascular drugs are made." ScienceDaily. ScienceDaily, 18 July 2012. <www.sciencedaily.com/releases/2012/07/120718131742.htm>.
Sanford-Burnham Medical Research Institute. (2012, July 18). Discovery of new heart failure trigger could change the way cardiovascular drugs are made. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2012/07/120718131742.htm
Sanford-Burnham Medical Research Institute. "Discovery of new heart failure trigger could change the way cardiovascular drugs are made." ScienceDaily. www.sciencedaily.com/releases/2012/07/120718131742.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins