BioEd Online

Some people suffer from heart disease even if they take precautionary measures such as avoiding high-cholesterol foods. Part of the solution to this puzzle is supplied by a team that studied mice with clogged arteries.

As the cells in blood-vessel walls grow old, their energy-generating machinery begins to leak, says the team. This releases reactive molecules into the vessels, triggering a chain of reactions that ultimately clogs up arteries and increases the risk of having a heart attack.

The scientists believe their results could lead to improvements in dietary recommendations designed to combat the artery-clogging disease atherosclerosis, a major form of heart disease.

Cutting cholesterol from one’s diet does not always prevent cardiovascular problems, says endocrinologist Clay Semenkovich of the Washington University School of Medicine in St. Louis, Missouri. “Probably the majority of people who have heart attacks have a normal cholesterol level," he says. "That suggests that there is something more going on."

Bad batteries

Semenkovich and his colleagues looked more closely at the cells making up blood-vessel walls to examine other possible causes of atherosclerosis.

Inside each cell, a tiny compartment called the mitochondrion churns out compounds that carry stored energy in their chemical bonds. With age, these generators become less efficient and leak an extremely reactive form of oxygen into the rest of the cell, Semenkovich explains. The oxygen escapes after molecules called uncoupling proteins, found in the mitochondrion's membrane, start to let electrical charge flow across the membrane.

The research team genetically engineered mice to have especially leaky mitochondria in their blood vessel cells. It found that although normal mice very rarely acquire atherosclerosis, the mutant mice all developed the disease, even when fed on a low-fat, low-cholesterol diet. The results of the experiment appear this week in Nature¹

Deadly repair

The researchers think that the leaky mitochondria in ageing blood-vessel cells could trigger a fatal accumulation of the plaques that block arteries in atherosclerosis.

They speculate that an increased flow of reactive oxygen damages the blood vessel's walls. The body then mounts an immune response to repair this damage, and scientists have already established that cells trying to fix arterial damage can create problems. These immune cells attract a form of cholesterol that sticks to arterial walls, forming plaques.

It is unclear why some people should be particularly prone to leaky mitochondria, but Semenkovich suggests that it may be linked to low levels of certain fatty acids. Other researchers have found that damaged areas of blood vessels seem to coincide with an absence of these fatty acids in the tissue.

He adds that more research is needed to find out whether components of fish oil, such as omega-3 fatty acids, could help to protect people against leaky mitochondria.