‘Zombie cells’ clog arteries

It’s no secret that our immune system seems to do more harm than good sometimes – just ask anyone with bad allergies – but the cells supposed to defend us from pathogens can clog up our arteries too, according to a mouse study.

Research by Bennett Childs from the Mayo Medical Clinic in the US and colleagues and published in the journal Science shows how ageing macrophages – white blood cells that combat infection and clean up damaged or dying cells – are directly linked to early and late stages of atherosclerosis.

The “senescent” macrophages are the culprits – cells that have stopped dividing but do not die, and sometimes called ‘zombie cells’ – which accumulate on the inside surface of blood vessels.

This knowledge could contribute to better prevention and treatment of the disease, which affects millions of people around the world and can lead to blood clots, heart attacks and stroke, says Stephen Nicholls, a cardiologist at the University of Adelaide in Australia who was not involved with the study.

“[It is a] really nice example of some work that is trying to understand the biology so that we ultimately lead to better treatments for our patients.

“In my clinical duties atherosclerosis represents a lot of the people that we see.

“It can have a very sudden and very short clinical expression, say in the form of sudden death, or in some patients it may actually have a recurrent expression over multiple years or even decades.”

While previous studies had linked plaque buildup with cell senescence, no one knew if zombie cells actively contributed to atherosclerosis – and at which stage.

So Childs and her crew took atherosclerosis-prone mice that had also been genetically engineered, so if they were administered a particular drug, their zombie cells were eliminated.

When the mice were fed a high-fat diet and given the drug, the researchers found that they displayed 60% less plaque than their control counterparts who still had full senescence, despite similar feeding habits and blood lipids (fatty substances in the blood).

Closer examination showed fatty streaks in the arteries of the control mice, which appeared shortly after the high-fat diets started.

 

These streaks contained fat-filled or “foamy” macrophages which pump out molecules called cytokines that stimulate inflammation.

But the arteries of mice without zombie cells, on the other hand, had far fewer fatty streaks – and less inflammation.

Childs and her team also found that the markers of plaque instability that accompany advanced atherosclerosis were significantly lower in the mice that had been given the senescence-suppressing drug than in those that did not.

Blocking senescent cells could benefit people at both early and late stages of the condition, and Nicholls notes that Childs’ work could be helpful in narrowing the scope of inflammatory cells that might be targeted to prevent and treat atherosclerosis down the track.

“One of the fields where there is a huge amount of interest at the moment is: should we be targeting something about inflammation?” he says.

“The problem with that is inflammation is quite a broad field, so we have to try and identify what we think is going to be the biggest bang for our buck in terms of targeting.”