Referral Notes:

  • Kathryn J. Moore, PhD, and her group have helped reveal that macrophages recognize and internalize cholesterol using the same receptors they use to detect bacteria, and that microRNA-33 is a key regulator of macrophage cholesterol efflux.
  • These discoveries helped define immune pathways that drive atherosclerotic plaque progression and represent potential therapeutic targets.
  • The same inflammatory pathways have since been implicated in lupus, psoriasis, and other autoimmune diseases.

For decades, heart disease was viewed largely as a plumbing problem, with arteries gradually narrowed by cholesterol buildup. Then, Kathryn J. Moore, PhD, helped illuminate something else at work: certain immune pathways treat those fatty deposits like a chronic infection. That inflammatory assault, mounted over decades, can lead to heart attack or stroke.

In an episode of NYU Langone Heath’s Behind the Breakthrough video series, Dr. Moore, the Jean and David Blechman Professor of Cardiology and director of the Cardiovascular Research Center, describes how this evolving understanding of atherosclerosis helped expand cardiovascular prevention beyond lipid lowering to include the present day interest in quieting the immune response underlying plaque growth.

Watch the video above to hear Dr. Moore discuss these key discoveries. Then read on to learn more about the science, its impact, and where Dr. Moore’s research is headed next.

‘Good Deed Gone Bad’

Within this inflammatory framework, macrophages play a central role in lesion progression. In atherosclerosis, macrophages accumulate in the artery wall to clear low-density lipoproteins (LDLs). But after taking up LDL, these macrophages can become cholesterol-laden, functionally impaired, and trapped within the plaque. “A good deed gone bad” is how Dr. Moore describes this process, as trapped macrophages recruit additional immune cells and sustain chronic inflammation.

“It’s that chronic, low-grade inflammation that drives plaque formation in the arteries over decades, leading to atherosclerosis,” Dr. Moore says.

It was Dr. Moore’s 2010 publication in Nature Immunology that helped reveal the mechanism underlying this inflammatory pathway. The study showed that macrophages recognize and take up cholesterol using the same receptors as they use to detect bacteria: toll-like receptors (TLRs).

Later that year, in a paper published in Science, her group showed that microRNA-33 (miR-33) plays a central role in suppressing genes required for cholesterol efflux from macrophages. The team subsequently designed inhibitors to block miR-33 in mice and reported in The Journal of Clinical Investigation that doing so improved cholesterol efflux from macrophages, raised levels of “good” high density lipoprotein (HDL), and reversed plaque buildup. They then recapitulated several of these findings in nonhuman primates in a study published in Nature.

Collectively, the work helped launch the field of miRNA regulation of lipoprotein metabolism and pointed toward therapies aimed at directly reversing the inflammatory pathways driving plaque progression.

Beyond Cardiovascular Disease

The discoveries have extended beyond cardiology. Collaborating with clinicians across NYU Langone, Dr. Moore has explored how the same immune pathways influence conditions such as lupus and psoriasis.

“We were surprised to find that pathways that we identified in the management of cholesterol also play important roles in regulating the inflammatory response in autoimmune conditions,” she says. The overlap hints at therapies that could address multiple inflammatory diseases at once—an approach that continues to shape Dr. Moore’s ongoing research.

Dr. Moore’s contributions have drawn international recognition. She is a member of the National Academy of Sciences and recipient of the 2024 Grand Prix Scientifique de la Fondation Lefoulon-Delalande, one of the highest global honors in cardiovascular research.