Ryohei Kaseda1, Kathy Jabs1, Tracy E Hunley1, Deborah Jones1, Aihua Bian2, Ryan M Allen3, Kasey C Vickers3, Patricia G Yancey3, MacRae F Linton4, Sergio Fazio5, Valentina Kon6. 1. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN. 2. Department of Statistics, Vanderbilt University Medical Center, Nashville, TN. 3. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. 4. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN. 5. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; Department of Pathology, Vanderbilt University Medical Center, Nashville, TN. 6. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN. Electronic address: valentina.kon@vanderbilt.edu.
Abstract
OBJECTIVES: Our aim was to determine if chronic kidney disease (CKD) occurring in childhood impairs the normally vasoprotective functions of high-density lipoproteins (HDLs). MATERIALS AND METHODS: HDLs were isolated from children with end-stage renal disease on dialysis (ESRD), children with moderate CKD and controls with normal kidney function. Macrophage response to HDLs was studied as expression of inflammatory markers (MCP-1, TNF-α, IL-1β) and chemotaxis. Human umbilical vein endothelial cells were used for expression of adhesion molecules (ICAM-1, VCAM-1, E-selectin) and adhesion. Cellular proliferation, apoptosis, and necrosis of endothelial cells were measured by MTS/PMS reagent-based assay, flow cytometry, and ELISA. Cholesterol efflux was assessed by gas chromatographic measurements of cholesterol in macrophages exposed to HDLs. RESULTS: Compared with HDL(Control), HDL(CKD) and HDL(ESRD) heightened the cytokine response and disrupted macrophage chemotaxis. HDL(Control) reduced endothelial expression of ICAM-1, VCAM-1, E-selectin, whereas HDL(CKD) and HDL(ESRD) were less effective and showed reduced capacity to protect endothelial cells against monocyte adhesion. Compared with a dramatically enhanced endothelial proliferation following injurious stimulus by HDL(Control), neither HDL(CKD) nor HDL(ESRD) caused proliferative effects. HDLs of all three groups were equally protective against apoptosis assessed by flow cytometry and cleaved caspase-3 activity. Compared to HDL(Control), HDL(CKD) and HDL(ESRD) trended toward reduced capacity as cholesterol acceptors. CONCLUSION: CKD in children impairs HDL function. Even in the absence of long-standing and concomitant risk factors, CKD alters specific HDL functions linked to control of inflammation and endothelial responses.
OBJECTIVES: Our aim was to determine if chronic kidney disease (CKD) occurring in childhood impairs the normally vasoprotective functions of high-density lipoproteins (HDLs). MATERIALS AND METHODS: HDLs were isolated from children with end-stage renal disease on dialysis (ESRD), children with moderate CKD and controls with normal kidney function. Macrophage response to HDLs was studied as expression of inflammatory markers (MCP-1, TNF-α, IL-1β) and chemotaxis. Human umbilical vein endothelial cells were used for expression of adhesion molecules (ICAM-1, VCAM-1, E-selectin) and adhesion. Cellular proliferation, apoptosis, and necrosis of endothelial cells were measured by MTS/PMS reagent-based assay, flow cytometry, and ELISA. Cholesterol efflux was assessed by gas chromatographic measurements of cholesterol in macrophages exposed to HDLs. RESULTS: Compared with HDL(Control), HDL(CKD) and HDL(ESRD) heightened the cytokine response and disrupted macrophage chemotaxis. HDL(Control) reduced endothelial expression of ICAM-1, VCAM-1, E-selectin, whereas HDL(CKD) and HDL(ESRD) were less effective and showed reduced capacity to protect endothelial cells against monocyte adhesion. Compared with a dramatically enhanced endothelial proliferation following injurious stimulus by HDL(Control), neither HDL(CKD) nor HDL(ESRD) caused proliferative effects. HDLs of all three groups were equally protective against apoptosis assessed by flow cytometry and cleaved caspase-3 activity. Compared to HDL(Control), HDL(CKD) and HDL(ESRD) trended toward reduced capacity as cholesterol acceptors. CONCLUSION: CKD in children impairs HDL function. Even in the absence of long-standing and concomitant risk factors, CKD alters specific HDL functions linked to control of inflammation and endothelial responses.
Authors: Daniel E Weiner; Hocine Tighiouart; Essam F Elsayed; John L Griffith; Deeb N Salem; Andrew S Levey; Mark J Sarnak Journal: Am J Kidney Dis Date: 2008-02 Impact factor: 8.860
Authors: Maureen McMahon; Jennifer Grossman; Brian Skaggs; John Fitzgerald; Lori Sahakian; Nagesh Ragavendra; Christina Charles-Schoeman; Karol Watson; Weng Kee Wong; Elizabeth Volkmann; Weiling Chen; Alan Gorn; George Karpouzas; Michael Weisman; Daniel J Wallace; Bevra H Hahn Journal: Arthritis Rheum Date: 2009-08
Authors: Adriana Hung; Lara Pupim; Chang Yu; Ayumi Shintani; Edward Siew; Carlos Ayus; Raymond M Hakim; Talat Alp Ikizler Journal: Hemodial Int Date: 2008-04 Impact factor: 1.812
Authors: Caroline S Fox; Kunihiro Matsushita; Mark Woodward; Henk J G Bilo; John Chalmers; Hiddo J Lambers Heerspink; Brian J Lee; Robert M Perkins; Peter Rossing; Toshimi Sairenchi; Marcello Tonelli; Joseph A Vassalotti; Kazumasa Yamagishi; Josef Coresh; Paul E de Jong; Chi-Pang Wen; Robert G Nelson Journal: Lancet Date: 2012-09-24 Impact factor: 79.321
Authors: Adriana M Hung; Yohei Tsuchida; Kristen L Nowak; Sudipa Sarkar; Michel Chonchol; Victoria Whitfield; Natjalie Salas; Anna Dikalova; Patricia G Yancey; Jiansheng Huang; MacRae F Linton; T Alp Ikizler; Valentina Kon Journal: Clin J Am Soc Nephrol Date: 2019-04-23 Impact factor: 8.237