Reverse cholesterol transport is a process whereby accumulated cholesterol is removed from tissues, including the artery wall, and transported back to the liver for excretion. Little is known about how cholesterol is removed from peripheral tissues, but a better understanding of these mechanisms could help in the development of therapies that treat atherosclerosis and other cholesterol-related disorders. Catherine Martel and colleagues examined the role of the lymphatic system in RCT. The lymphatic system generally mediates transport of large molecules from the area around blood vessels into the blood. Randolph and colleagues tracked RCT in a mouse model of atherosclerosis with normal and impaired lymphatic growth. Mice lacking normal lymphatic growth retained more cholesterol in their aortas, indicating that lymphatic vessels are required for RCT in the aortic wall. The accompanying image on the left shows the descending aorta (green) wrapped with lymphatic vessels (purple). The inset and image on the right shows lymphatic vessels (bright areas) around the aortic arch.
Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin — 1 surgical and the other genetic — to quantitatively track RCT following injection of [3H]-cholesterol–loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic
Catherine Martel, Wenjun Li, Brian Fulp, Andrew M. Platt, Emmanuel L. Gautier, Marit Westerterp, Robert Bittman, Alan R. Tall, Shu-Hsia Chen, Michael J. Thomas, Daniel Kreisel, Melody A. Swartz, Mary G. Sorci-Thomas, Gwendalyn J. Randolph