The heat that hurts  pg. 2

Colorized microscopic image shows monocytes “diving” into an atherosclerotic lesion in the lining of a blood vessel. The monocytes have been “activated” by inflammatory signals on the blood vessel lining. Arm-like pseudopods drag the monocytes into the gaps between endothelial cells and down into the atherosclerotic plaque beneath the endothelium. Here they become macrophages, vacuum up excess lipid and add to the size of the plaque.
Image courtesy of Jay Jerome, Ph.D., director of the Research Electron Microscopy Resource at Vanderbilt; colorization by Deborah Doyle
Linton and Fazio decided early in their careers to take a team approach to their research. Since joining the faculty at Vanderbilt in 1993 (Fazio is a professor of Medicine and Pathology), they have published several seminal papers in the field of atherosclerosis, and they co-direct the medical center’s Atherosclerosis Research Unit.

In one of their highest profile papers, published in the journal Science in 1995, Fazio, Linton and James Atkinson, M.D., Ph.D., professor of Pathology, reported that apolipoprotein E (apoE), a protein important in lipoprotein metabolism, seemed to protect mice from developing atherosclerosis.

The largest supply of apoE comes from the liver, Linton says. But the protein is also made by macrophages, and thus may participate in the inflammatory response.

To determine what, if any, role apoE expressed in macrophages played in the development of atherosclerosis, Linton and Fazio studied a strain of mice that lacked both copies of the apoE gene. These mice develop significant atherosclerosis, unlike their genetically normal—or wild type—counterparts. The researchers irradiated the apoE deficient mice to kill their bone marrow, the source of macrophages, then gave them transplants of bone marrow cells from wild type mice.

Mice deficient in apoE that received the transplants did not develop atherosclerotic plaques. “The small amount of apoE that came from the bone marrow was enough to cure the mice,” says Linton.

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