Treating heart attacks with HDL cholesterol particles

A cholesterol injection can reduce the damage done by a heart attack, new research has shown.
12 October 2017


An injection of the particles that carry cholesterol can reduce the damage done by a heart attack, new research has shown.

For years cholesterol has been condemned as the metabolic bad boy responsible for furring up arteries and causing heart attacks and strokes. And the statin family of drugs, one of the mainstays of cardiac risk reduction, work by blocking the synthesis of cholesterol in cells to cut blood cholesterol levels. This, doctors think, helps to reduce the rate at which arterial disease progresses.

But not all forms of cholesterol are evil. The damage, in fact, is done mainly by lower density forms of cholesterol called LDLs. Its higher density counterpart - High Density Lipoprotein (HDL) cholesterol - on the other hand, is protective against heart disease. And the higher the HDL level in the bloodstream (up to a point), the lower the risk of vascular disease.

This has formed the basis of a number of clinical trials, which have explored whether medically elevating the blood level of HDL can reduce heart attack rates. Unfortunately the results have been disappointing. But this does mean that there are HDL preparations available in the clinic for further testing, and now scientists have discovered that, administered just after a heart attack, an HDL injection can dramatically reduce the injury sustained by the heart.

Sarah Heywood, from the Baker Heart and Diabetes Institute in Melbourne, Australia, has found that the size of the scar that develops in the aftermath of an MI (myocardial infarction) can be reduced by 20% if experimental mice receive an HDL infusion. This reduction in scar formation is mirrored by improved blood vessel density in the injured tissue, a reduction in the subsequent formation of stiff, fibrous tissue, and overall improved heart function compared with untreated control animals.

Presented in the journal Science Translational Medicine this week, the results show that HDL administered immediately after an MI boosts glucose uptake and utlisation by heart muscle cells, resulting in improved cell viability and a reduced likelihood of subsequent heart failure.

Heywood's data suggest that HDL particles themselves engage with a signaling receptor called Akt, which is expressed on the surfaces of heart cells. The interaction with HDL activates the receptor, which is chemically "wired up" to many of the same metabolic pathways in the cell that are normally activated by the sugar-controlling hormone insulin. These pathways include enzymes that promote the burning of glucose to produce energy that the cell can use.

Getting glucose into threatened heart cells like this, Heywood thinks, is critical to their survival. "The interruption of the blood flow deprives the cells of food, so they run out of energy and they die. HDL increases the amount of glucose that can get into the cells, providing them with more energy, so more of them remain viable." 

This is an entirely new aspect of HDL biology with a unique and novel therapeutic facet, and Heywood is very optimistic about its prospects.

"Because there are already two HDL preparations going through clinical trials at the moment, albeit for a different therapeutic purpose, it should be possible to translate this work to humans quite rapidly," she says.


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