Metabolic study in mice could lead to 'good cholesterol' boosters

Aug 07, 2007

Researchers have identified a new player in the control of so-called “good” cholesterol that circulates in the bloodstream and reduces heart attack risk, according to a report in the August issue of Cell Metabolism, a publication of Cell Press.

Should the metabolic pathway uncovered in mice operate similarly in humans, the new discovery could point the way to therapies that protect against heart disease by boosting concentrations of the beneficial high-density lipoprotein cholesterol (HDL-C).

“By and large, the medicines now available lower levels of the ‘bad’ low-density lipoprotein cholesterol [LDL-C],” said Weijun Jin of the University of Pennsylvania School of Medicine. “There is a great need for methods to raise good cholesterol levels. Our findings suggest there may be multiple places to interrupt the metabolism of HDL-C.”

LDL-C can build up in blood vessel walls, increasing the risk of heart disease or stroke. By contrast, HDL-C tends to carry cholesterol away from the arteries to the liver—a process known as reverse cholesterol transport—where it is broken down and then eliminated from the body.

Existing LDL-C-lowering drugs such as statins can reduce the risk of heart attack by 20 to 35 percent, Jin said. However, treatment methods that would simultaneously lower bad cholesterol and increase good cholesterol have the potential to work even better. Indeed, researchers believe that increasing HDL-C while lowering LDL-C might cut heart attack risk by as much as 70 percent, he explained.

In the current study, the researchers found that treatments that partially block the activity of liver enzymes called proprotein convertases decreased plasma HDL-C levels in mice. They showed that the metabolic effect of the proprotein convertases depended on yet another factor, an enzyme called endothelial lipase (EL), which breaks down HDL-C. Proprotein convertases normally reduce EL function, they reported. Thus, the loss of proprotein convertase activity leads to an increase in EL and a decline in HDL-C.

Likewise, they showed that increased activity of proprotein convertases in the liver gives a significant boost to the protective HDL-C.

“Proprotein convertases are an unexpected new player in HDL-C metabolism,” Jin said. “By manipulating levels of the enzyme in both directions, we were able to reduce HDL-C to almost nothing or double it.” That wide range of effects suggests that it may be “theoretically possible to manipulate good cholesterol levels to whatever point you like.”

He emphasized, however, that the new findings represent basic research in animals. Further investigation will examine to what extent the pathway is preserved in humans, Jin said. The authors will also look for chemicals capable of modifying the pathway, which could hold promise as new good-cholesterol-boosting drugs.

Source: Cell Press

Explore further: US scientists make embryonic stem cells from adult skin

add to favorites email to friend print save as pdf

Related Stories

Egypt archaeologists find ancient writer's tomb

2 hours ago

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Ex-Apple chief plans mobile phone for India

2 hours ago

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

NASA's space station Robonaut finally getting legs

2 hours ago

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Health care site flagged in Heartbleed review

15 hours ago

People with accounts on the enrollment website for President Barack Obama's signature health care law are being told to change their passwords following an administration-wide review of the government's vulnerability to the ...

Airbnb rental site raises $450 mn

15 hours ago

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.

Recommended for you

Leeches help save woman's ear after pit bull mauling

Apr 18, 2014

(HealthDay)—A pit bull attack in July 2013 left a 19-year-old woman with her left ear ripped from her head, leaving an open wound. After preserving the ear, the surgical team started with a reconnection ...

New pain relief targets discovered

Apr 17, 2014

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

User comments : 0

More news stories

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Study says we're over the hill at 24

(Medical Xpress)—It's a hard pill to swallow, but if you're over 24 years of age you've already reached your peak in terms of your cognitive motor performance, according to a new Simon Fraser University study.

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.