Coronary artery disease (or CAD), responsible for half the deaths in the U.S., may be less a product of too many cheeseburgers and more the result of a particular kind of immune cell’s sweet tooth and its postprandial temper tantrum.
The discovery of this connection is outlined in a study published in the Journal of Experimental Medicine, which summarizes a series of experiments conducted by Stanford immunologist Connie Weyand, MD, and her colleagues.
The new findings support a growing recognition that it’s not just the arterial deposition of fatty materials called lipids that causes CAD and subsequent heart attacks, but also underlying chronic inflammation.
While lipids are indeed a prime constituent of the arterial deposits called plaque, it’s now understood that plaque also contains immune cells — chiefly, a type called macrophages.
Macrophages generally fall into two broad categories, as I wrote in a news release about the study:
The kinder, gentler ones — so-called M2 macrophages — are like construction engineers, nibbling cellular detritus left behind from a wound or infection, releasing factors that encourage new cell growth and stimulate blood flow, and otherwise overseeing tissue repair. So-called M1 macrophages, on the other hand, are inflammatory: [T]hey blow the whistle on pathogens, recruiting other types of immune cells to the scene. [T]hey attack the invaders themselves by spitting out nasty little clouds of biohazardous chemicals called free radicals. And they squirt out proteins that act both locally and systemically to ramp up the entire immune system to high-alert status.
Inflammatory resident macrophages' constant cranky disposition renders arterial plaque increasingly brittle, until a chunk of it breaks off, suddenly and seriously blocking blood flow. And that's a heart attack, folks.
In the study, Weyand and her associates compared macrophages from patients with documented CAD (each had had at least one heart attack) with those from healthy subjects. They measured the macrophages' output of IL-6, a substance that gooses the entire immune system (including the macrophages themselves) into inflammatory overdrive, and found that CAD patients' macrophages were producing much more of it than healthy subjects' macrophages were.
The scientists ultimately found that the hyperproduction of IL-6 in CAD patients' macrophages was the result of a defect that caused them to suck up glucose from circulating blood at an exaggerated rate and pig out on it.
It wasn't just a matter of too much sugar floating around in the blood, as happens among diabetics and, for that matter, among the one-third of all American adults with metabolic syndrome: a constellation of conditions including oversize waistlines, high blood pressure and low "good cholesterol" levels. Healthy subjects' macrophages, immersed in glucose-rich solutions, didn't boost their glucose metabolism or IL-6 output.
The researchers learned, instead, that the macrophages of people at risk of developing CAD are predisposed to hypermetabolize glucose.
The good news: Impeding any of several steps in this biochemical pathway all succeeded in shutting down CAD-associated macrophages' inflammatory activity. The search is on for safe drugs that do similar things.
Meanwhile, people getting lab tests for cardiovascular-health purposes should ask their doctor to check the box for C-reactive protein or CRP, which Weyand told me is a good proxy for underlying IL-6 levels and is an independent risk factor for heart disease. The statin drugs millions now take to optimize their lipid levels have been shown to also reduce the systemic inflammation flagged by elevated CRP — this decreases heart-attack risk even in patients whose lipid levels are normal.
Previously: Important metabolic defect identified in immune cells of rheumatoid arthritis patients, New arterial insights portend potential treatments for life-threatening diseases and Did microbes mess with Typhoid Mary's macrophages?
Photo by Anthony DeLorenzo
