Featured Research

from universities, journals, and other organizations

Protein tug of war points toward better therapies for cardiovascular disease

Date:
November 15, 2012
Source:
Georgia Health Sciences University
Summary:
Two proteins are in a tug of war that determines how much the body makes of superoxide, a highly reactive and potentially destructive product of oxygen that's dramatically elevated in cardiovascular disease, researchers report. Their finding indicates an antiulcer drug just may help the body reduce excessive levels.

Two proteins are in a tug of war that determines how much the body makes of superoxide, a highly reactive and potentially destructive product of oxygen that's dramatically elevated in cardiovascular disease, researchers report.

Related Articles


Their finding indicates an antiulcer drug just may help the body reduce excessive levels.

Hsp90 and Hsp70 are both heat shock proteins but appear to have opposite effects on reactive oxygen species production, said Dr. David J.R. Fulton, Interim Director of the Vascular Biology Center at the Medical College of Georgia at Georgia Health Sciences University.

"Our studies show that Hsp90 promotes the activity of Nox enzymes, the source of reactive superoxide and all of the reactive oxygen species that descend from it, while Hsp70 has an opposing action that inhibits Nox," Fulton said.

When researchers gave Hsp90 inhibitors, the binding of Nox enzymes to Hsp90 was reduced, its binding to Hsp70 increased and reactive oxygen species production decreased. The inhibitors also reduced reactive oxygen species production in blood vessels from obese mice, where it contributes to the loss of elasticity and narrowing that are hallmarks of cardiovascular disease. While Hsp90 inhibition was known to suppress inflammation and reduce cardiovascular damage, just how it made these positive changes was unknown.

The yin and yang the researchers found points toward a targeted therapy that should give Hsp70 the edge, said Dr. Feng Chen, postdoctoral fellow. Chen is first author of the study in the American Heart Association journal Arteriosclerosis, Thrombosis and Vascular Biology.

Hsp90 inhibitors are used to treat cancer, which depends on Hsp90 to support rapid cell division. But they also target proteins that help blood vessels relax, such as nitric oxide synthase, so probably are not a good choice in cardiovascular disease. "Cardiovascular disease is a chronic disease, and we want to minimize negative side effects while providing protection," Fulton said.

In this case, a better approach appears to be directly increasing the expression of Hsp70 with a drug such as geranylgeranylacetone, or GGA, an antiulcer drug used in Japan with relatively few side effects, Chen said. When the MCG researchers treated human aortic vascular smooth muscle cells with the drug, for example, Hsp70's binding to Nox increased while Nox's ability to generate superoxide decreased.

Next steps include looking at whether this increased expression of Hsp70 actually translates to healthier blood vessels in a cardiovascular model. "If we can upregulate Hsp70 without affecting nitric oxide synthase, it should," said Fulton, the study's corresponding author.

Hsp70 and 90 are chaperones that guide protein folding in different ways and can influence more than just whether Nox enzymes are stable or degraded. Hsp70 levels are regulated by the molecule heat shock factor, which is bound to and repressed by Hsp90. That's one reason why Hsp90 inhibitors increase Hsp70 levels.

Reactive oxygen species are not all bad, the researchers noted. At normal levels, they aid cell signaling and homeostasis as well as the mounting of an immune response. However, excessive levels associated with chronic inflammation are thought to accelerate cardiovascular disease. "A little bit is good; you want a well-honed immune system to fend of pathogens," Fulton said. "Chronic inflammation is the problem."

The researchers completed their studies in normal and diabetic mice -- diabetes increases the risk of cardiovascular disease by at least 50 percent -- as well as the saphenous, or major superficial leg veins, of patients with cardiovascular disease.

Cardiovascular disease is the leading cause of death in the United States, according to the Centers for Disease Control and Prevention. The research was funded by the National Institutes of Health and the American Heart Association.


Story Source:

The above story is based on materials provided by Georgia Health Sciences University. The original article was written by Toni Baker. Note: Materials may be edited for content and length.


Journal Reference:

  1. F. Chen, Y. Yu, J. Qian, Y. Wang, B. Cheng, C. Dimitropoulou, V. Patel, A. Chadli, R. D. Rudic, D. W. Stepp, J. D. Catravas, D. J. R. Fulton. Opposing Actions of Heat Shock Protein 90 and 70 Regulate Nicotinamide Adenine Dinucleotide Phosphate Oxidase Stability and Reactive Oxygen Species Production. Arteriosclerosis, Thrombosis, and Vascular Biology, 2012; 32 (12): 2989 DOI: 10.1161/ATVBAHA.112.300361

Cite This Page:

Georgia Health Sciences University. "Protein tug of war points toward better therapies for cardiovascular disease." ScienceDaily. ScienceDaily, 15 November 2012. <www.sciencedaily.com/releases/2012/11/121115133529.htm>.
Georgia Health Sciences University. (2012, November 15). Protein tug of war points toward better therapies for cardiovascular disease. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2012/11/121115133529.htm
Georgia Health Sciences University. "Protein tug of war points toward better therapies for cardiovascular disease." ScienceDaily. www.sciencedaily.com/releases/2012/11/121115133529.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
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
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