December 2019 Discover CircRes Discover CircRes

This month on Episode 7 of the Discover CircRes podcast, host Cindy St. Hilaire highlights two featured articles from the December 6, 2019 issue of Circulation Research and talks with Roy Silverstein and Yiliang Chen about their article, Mitochondrial Metabolic Reprogramming by CD36 Signaling Drives Macrophage Inflammatory Responses.
Article highlights:

McArdle, et al, et al. Migratory and Dancing Atherosclerotic Macrophages
Skaria, et al. Cardioprotection with Endogenous αCGRP
Transcript

Dr Cindy St. Hilaire: Hi, welcome to Discover CircRes the monthly podcast of the American Heart Association journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire, and I'm an Assistant Professor at the University of Pittsburgh. In this episode I'm going to share with you highlights from recent articles published in the December 6 issue of Circulation Research. We're also going to have an in-depth conversation with Drs Roy Silverstein and Yiliang Chen about their recent article on how macrophage CD36 modulates immunometabolism. Also, the American Heart Association Scientific Sessions were recently held in Philadelphia, PA and in this edition of Discover CircRes, we're going to feature a conversation with the editors in chief of Circulation Research and Circulation, Drs Jane Friedman and Joe Hill.
The first article I'd like to highlight is titled Migratory Dancing Atherosclerotic Macrophages. The first author is Sarah McCardell and the corresponding author is Klaus Ley and the work was conducted at the La Jolla Institute of Immunology in La Jolla, California. A major component of atherosclerosis is the inflammatory response and atherosclerotic plaques contain a mix of macrophages. Some macrophages arise from proliferation of resident cells, while other macrophages can infiltrate in from the blood. And a few studies have shown that smooth muscle cells can acquire some macrophage-like markers. Some macrophages are anti-inflammatory while others are more pro-inflammatory. These variations have largely been determined using techniques that examine the cell surface marker expression, the transcription profiles, or by mass spectrometry. But how all these different types of macrophagia cells look and function in vivo has not been clearly defined nor visualized. McCardell and colleagues have now observed fluorescently-labeled macrophages in the atherosclerotic plaques of live mice.
First, using single cell RNA sequencing, they identified key markers of macrophage subsets. These markers are Cx3cr1 and CD11c. They then generated Apoe knockout mice that could then express green fluorescent protein under the direction of the Cx3cr1 promoter and yellow fluorescent protein under the direction of CD11c. These fluorescent proteins could be expressed individually, they could be expressed together, or they could be expressed not at all. And then in these mice they used intravital microscopy to look at the carotid artery plaques and they found while green cells and double positive cells, so that is, cells expressing Cx3cr1or both Cx3cr1 and CD11c--these cells tended to stay in one place, but they could extrude these protrusions akin to dancing, while the yellow cells or the cells that were expressing CD11c alone were more spherical and migratory.
RNA analysis revealed that migratory genes were indeed upregulated in the yellow cells as compared to the green cells. The work provides preliminary insights into plaque macrophage dynamics and presents a technical resource for investigating how such behaviors may influence disease progression and I highly recommend you check this article out online. They have included several videos in the supplementary data and they're really beautiful. You can actually see the macrophages moving around and dancing and moving through the tissue and it's really neat to think about maybe how people are going to use this in the future to study the role of macrophages and maybe even other inflammatory cells in