Scientists Stimulate Immune System to Fight Heart Disease
Marcophages are the garbage men of the body. These immune system cells mop up cellular toxins and debris that are produced through cells' normal functioning.
But scientists at Washington University School of Medicine in St. Louis wondered, what if macrophages could be pressed into service to eliminate or degrade the accumulation of plaque as well? The fatty substance collects inside blood vessels and is a leading cause of heart disease and stroke.
Cardiology researcher Babak Razani has pondered that possibility. "If you, you could imagine this, that you could somehow manipulate it to rev it up, to stimulate its function, then you could make a macrophage into a super-macrophage, one that’s really stimulated to degrade."
In a two-part study published in the journal Nature Communications, Razani and colleagues described how they manipulated and activated a genetic molecule called TFEB that goes into the nucleus of macrophages, supercharging their housekeeping skills inside cells.
Researchers then showed that a simple sugar, called trehalose, stimulated macrophages in the same way. In experiments with mice prone to atherosclerotic plaques, injection of the sugar molecule decreased plaque size by 30 percent.
"So that’s what we found here," Razani reports, "that this simple, natural compound, that is very safe, could be very atherogenic as therapy for cardiovascular disease."
In their unaltered state, macrophages try to fix damaged arteries by cleaning up cellular waste, including misshapen proteins, excess fat and dysfunction cellular structures called organelles.
But Razani says they eventually become overwhelmed by the task in people with atherosclerotic plaques, contributing to the debris problem that leads to inflammation and more disease.
Razani said supercharging macrophages with trehalose, so they resist damage and are able to continue their housekeeping function, offers a potential treatment for plaques, in addition to cholesterol-lowering drugs.
Because it’s a natural substance found in yeast, mushrooms and crustaceans, Razani said trehalose is completely safe.
Investigations found the sugar is broken down and doesn’t work when swallowed. Trehalose reduced the size of arterial plaques only when injected into mice. Other sugars did not have any effect.
So the challenge for researchers now is to find a way to turn trehalose into a form that is effective in humans to fight heart disease and possibly other health conditions like fatty liver disease and diabetes.