Lymphatic transport of high-density lipoproteins and chylomicrons

Abstract

The life cycles of VLDLs and most LDLs occur within plasma. By contrast, the role of HDLs in cholesterol transport from cells requires that they readily gain access to and function within interstitial fluid. Studies of lymph derived from skin, connective tissue, and adipose tissue have demonstrated that particles as large as HDLs require transport through lymphatics to return to the bloodstream during reverse cholesterol transport. Targeting HDL for therapeutic purposes will require understanding its biology in the extravascular compartment, within the interstitium and lymph, in health and disease, and we herein review the processes that mediate the transport of HDLs and chylomicrons through the lymphatic vasculature.

DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport

“…One of the primary roles of lacteals is the transport of dietary long-chain fatty acids, secreted from enterocytes in the form of lipoprotein particles called chylomicrons (59). To study chylomicron transport, we Representative whole-mount images of intestinal villus blood capillaries (PECAM1, green) and lacteals (LYVE1, red) after αVEGFR2 or αVEGFR3 treatment.…”

Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease

“…12 This dye, like other macromolecules within the interstitium, 11 was expected to be cleared from the tissue predominantly through the lymphatic vasculature and thus visibly label major lymphatic drainage from the mucosa. In regions deemed grossly normal, the dye cleared in a manner that would be expected, based on the anatomical location of mesenteric lymphatic collecting vessels that run anti-parallel to the intestinal wall as they drain to LNs 13 ( Figure 2A).…”

“…Indeed, creeping fat is a hallmark of the inflamed CD-affected tissue, but its etiology is unexplained. 10 One possibility connected to the discussion of lymphatic vessels is that creeping fat is driven by the spillage into the mesentery of the fatty chylomicrons carried in lymph 11 by highly permeable or leaky lymphatic vessels.…”

LDL and HDL transfer rates across peripheral microvascular endothelium agree with those predicted for passive ultrafiltration in humans

“…Studies of human afferent peripheral lymph have shown that the concentrations of apo AI and apo AII in normal human interstitial fl uid average about one-fi fth of those in plasma ( 4-6 ), while lymph apo B concentration averages only one-tenth ( 4, 7 ). The ratio of HDL to LDL particles in interstitial fl uid has been estimated to average about 50:1 in healthy humans ( 4,8 ).The striking differences in lipoprotein concentrations between plasma and interstitial fl uid, combined with their roles in atherosclerosis, highlight the importance of understanding the mechanisms by which they move into and out of the extravascular compartment. By analyzing data on adipokines of different molecular size, Miller et al ( 9 ) showed that the principal pathway by which a macromolecule leaves the interstitium of peripheral tissues in humans is determined by its size, the proportion leaving via capillaries decreasing and that via the lymphatic system increasing, as molecular radius rises.…”

“…Studies of human afferent peripheral lymph have shown that the concentrations of apo AI and apo AII in normal human interstitial fl uid average about one-fi fth of those in plasma ( 4-6 ), while lymph apo B concentration averages only one-tenth ( 4, 7 ). The ratio of HDL to LDL particles in interstitial fl uid has been estimated to average about 50:1 in healthy humans ( 4,8 ).…”