Kazuya Miyashita1, Isamu Fukamachi1, Manabu Nagao2, Tatsuro Ishida2, Junji Kobayashi3, Tetsuo Machida4, Kiyomi Nakajima4, Masami Murakami4, Michael Ploug5, Anne P Beigneux6, Stephen G Young7, Katsuyuki Nakajima8. 1. Immuno-Biological Laboratories, Fujioka, Gunma, Japan. 2. Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. 3. Department of General Internal Medicine, Kanazawa Medical University, Kanazawa, Ishikawa, Japan. 4. Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. 5. Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark. 6. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. 7. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. 8. Department of General Internal Medicine, Kanazawa Medical University, Kanazawa, Ishikawa, Japan; Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. Electronic address: nakajimak05@ybb.ne.jp.
Abstract
BACKGROUND: Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), a glycosylphosphatidylinositol (GPI)-anchored protein of capillary endothelial cells, transports lipoprotein lipase to the capillary lumen and is essential for the lipolytic processing of triglyceride-rich lipoproteins. OBJECTIVE: Because some GPI-anchored proteins have been detected in plasma, we tested whether GPIHBP1 is present in human blood and whether GPIHBP1 deficiency or a history of cardiovascular disease affected GPIHBP1 circulating levels. METHODS: We developed 2 monoclonal antibodies against GPIHBP1 and used the antibodies to establish a sandwich enzyme-linked immunosorbent assay (ELISA) to measure GPIHBP1 levels in human blood. RESULTS: The GPIHBP1 ELISA was linear in the 8 to 500 pg/mL range and allowed the quantification of GPIHBP1 in serum and in pre- and post-heparin plasma (including lipemic samples). GPIHBP1 was undetectable in the plasma of subjects with null mutations in GPIHBP1. Serum GPIHBP1 median levels were 849 pg/mL (range: 740-1014) in healthy volunteers (n = 28) and 1087 pg/mL (range: 877-1371) in patients with a history of cardiovascular or metabolic disease (n = 415). There was an extremely small inverse correlation between GPIHBP1 and triglyceride levels (r = 0.109; P < .0275). GPIHBP1 levels tended to be slightly higher in patients who had a major cardiovascular event after revascularization. CONCLUSION: We developed an ELISA for quantifying GPIHBP1 in human blood. This assay will be useful to identify patients with GPIHBP1 deficiency and patients with GPIHBP1 autoantibodies. The potential of plasma GPIHBP1 as a biomarker for metabolic or cardiovascular disease is yet questionable but needs additional testing.
BACKGROUND:Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), a glycosylphosphatidylinositol (GPI)-anchored protein of capillary endothelial cells, transports lipoprotein lipase to the capillary lumen and is essential for the lipolytic processing of triglyceride-rich lipoproteins. OBJECTIVE: Because some GPI-anchored proteins have been detected in plasma, we tested whether GPIHBP1 is present in human blood and whether GPIHBP1 deficiency or a history of cardiovascular disease affected GPIHBP1 circulating levels. METHODS: We developed 2 monoclonal antibodies against GPIHBP1 and used the antibodies to establish a sandwich enzyme-linked immunosorbent assay (ELISA) to measure GPIHBP1 levels in human blood. RESULTS: The GPIHBP1 ELISA was linear in the 8 to 500 pg/mL range and allowed the quantification of GPIHBP1 in serum and in pre- and post-heparin plasma (including lipemic samples). GPIHBP1 was undetectable in the plasma of subjects with null mutations in GPIHBP1. Serum GPIHBP1 median levels were 849 pg/mL (range: 740-1014) in healthy volunteers (n = 28) and 1087 pg/mL (range: 877-1371) in patients with a history of cardiovascular or metabolic disease (n = 415). There was an extremely small inverse correlation between GPIHBP1 and triglyceride levels (r = 0.109; P < .0275). GPIHBP1 levels tended to be slightly higher in patients who had a major cardiovascular event after revascularization. CONCLUSION: We developed an ELISA for quantifying GPIHBP1 in human blood. This assay will be useful to identify patients with GPIHBP1 deficiency and patients with GPIHBP1 autoantibodies. The potential of plasma GPIHBP1 as a biomarker for metabolic or cardiovascular disease is yet questionable but needs additional testing.
Authors: Anne P Beigneux; Kazuya Miyashita; Michael Ploug; Dirk J Blom; Masumi Ai; MacRae F Linton; Weerapan Khovidhunkit; Robert Dufour; Abhimanyu Garg; Maureen A McMahon; Clive R Pullinger; Norma P Sandoval; Xuchen Hu; Christopher M Allan; Mikael Larsson; Tetsuo Machida; Masami Murakami; Karen Reue; Peter Tontonoz; Ira J Goldberg; Philippe Moulin; Sybil Charrière; Loren G Fong; Katsuyuki Nakajima; Stephen G Young Journal: N Engl J Med Date: 2017-04-05 Impact factor: 91.245
Authors: Remco Franssen; Stephen G Young; Frank Peelman; Jozef Hertecant; Jeroen A Sierts; Alinda W M Schimmel; André Bensadoun; John J P Kastelein; Loren G Fong; Geesje M Dallinga-Thie; Anne P Beigneux Journal: Circ Cardiovasc Genet Date: 2010-02-02
Authors: Jun Eguchi; Kazuya Miyashita; Isamu Fukamachi; Katsuyuki Nakajima; Masami Murakami; Yuko Kawahara; Toru Yamashita; Yasuyuki Ohta; Koji Abe; Atsuko Nakatsuka; Mai Mino; Satoru Takase; Hiroaki Okazaki; Robert A Hegele; Michael Ploug; Xuchen Hu; Jun Wada; Stephen G Young; Anne P Beigneux Journal: J Clin Lipidol Date: 2018-10-24 Impact factor: 4.766
Authors: Kristian K Kristensen; Katrine Zinck Leth-Espensen; Haydyn D T Mertens; Gabriel Birrane; Muthuraman Meiyappan; Gunilla Olivecrona; Thomas J D Jørgensen; Stephen G Young; Michael Ploug Journal: Proc Natl Acad Sci U S A Date: 2020-02-07 Impact factor: 11.205
Authors: Kazuya Miyashita; Jens Lutz; Lisa C Hudgins; Dana Toib; Ambika P Ashraf; Wenxin Song; Masami Murakami; Katsuyuki Nakajima; Michael Ploug; Loren G Fong; Stephen G Young; Anne P Beigneux Journal: J Lipid Res Date: 2020-09-18 Impact factor: 5.922
Authors: Stephen G Young; Loren G Fong; Anne P Beigneux; Christopher M Allan; Cuiwen He; Haibo Jiang; Katsuyuki Nakajima; Muthuraman Meiyappan; Gabriel Birrane; Michael Ploug Journal: Cell Metab Date: 2019-07-02 Impact factor: 27.287