Dual Role of Circulating Angiopoietin-Like 4 (ANGPTL4) in Promoting Hypertriglyceridemia and Lowering Proteinuria in Nephrotic Syndrome Nosratola D.

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Dual Role of Circulating Angiopoietin-Like 4 (ANGPTL4) in Promoting Hypertriglyceridemia and Lowering Proteinuria in Nephrotic Syndrome Nosratola D. Vaziri, MD, MACP, Hamid Moradi, MD American Journal of Kidney Diseases Volume 64, Issue 4, Pages 495-498 (October 2014) DOI: 10.1053/j.ajkd.2014.04.016 Copyright © 2014 National Kidney Foundation, Inc. Terms and Conditions

Figure 1 Nascent very low-density lipoprotein (VLDL) particles are produced in hepatocytes (upper panel) and released into the circulation, where they acquire apolipoprotein E (Apo-E) and Apo-C from cholesterol ester (CE)-rich high-density lipoprotein (HDL) subfraction 2 (HDL-2). In capillaries perfusing muscle and adipose tissue, VLDL binds to the endothelial surface by its Apo-E content and activates the adjacent lipoprotein lipase (LPL) by its Apo-CII content. This leads to hydrolysis of VLDL's triglyceride (TG) cargo by LPL, release of free fatty acid (FFA), and conversion of VLDL to intermediate-density lipoprotein (IDL). In addition to the lipolytic pathway, a fraction of circulating VLDL is removed by a VLDL receptor (VLDLr)-mediated pathway. Nascent chylomicrons (lower panel) are formed in enterocytes and released into the circulation, where they acquire Apo-E and Apo-C from HDL-2. This is followed by LPL-mediated hydrolysis of their triglyceride contents and their conversion to chylomicron remnants. Abbreviations: CETP, cholesterylester transfer protein; GPIHBP1, glycosylphosphatidylinositol-anchored binding protein 1; LDLr, low-density lipoprotein receptor. American Journal of Kidney Diseases 2014 64, 495-498DOI: (10.1053/j.ajkd.2014.04.016) Copyright © 2014 National Kidney Foundation, Inc. Terms and Conditions

Figure 2 Nephrotic proteinuria results in elevation of plasma free fatty acid (FFA) to albumin ratio, which increases circulating angiopoietin-like 4 (Angptl4) level. By inhibition of lipoprotein lipase (LPL), upregulation of hormone-sensitive lipase, and interaction with glomerular capillary αvβ5 integrin, elevation of Angptl4 simultaneously promotes hypertriglyceridemia, depletion of adipose tissue triglyceride (TG) content, and attenuation of proteinuria. American Journal of Kidney Diseases 2014 64, 495-498DOI: (10.1053/j.ajkd.2014.04.016) Copyright © 2014 National Kidney Foundation, Inc. Terms and Conditions