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Cited by 364

The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.

An abundant dysfunctional apolipoprotein A1 in human atheroma

Open access
Huang, Ying, DiDonato, Joseph A, Levison, Bruce S, Schmitt, Dave, Li, Lin, Wu, Yuping, Buffa, Jennifer, Kim, Timothy, Gerstenecker, Gary S, Gu, Xiaodong, Kadiyala, Chandra S, Wang, Zeneng, Culley, Miranda K, Hazen, Jennie E, DiDonato, Anthony J, Fu, Xiaoming, Berisha, Stela Z, Peng, Daoquan, Nguyen, Truc T, Liang, Shaohong, Chuang, Chia-Chi, Cho, Leslie, Plow, Edward F, Fox, Paul L, Gogonea, Valentin, Tang, W H Wilson, Parks, John S, Fisher, Edward A, Smith, Jonathan D, Hazen, Stanley L·2014·Nature Medicine
DOI 10.1038/nm.3459
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Abstract

Recent studies have indicated that high-density lipoproteins (HDLs) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma are dysfunctional and are extensively oxidized by myeloperoxidase (MPO). In vitro oxidation of either apoA1 or HDL particles by MPO impairs their cholesterol acceptor function. Here, using phage display affinity maturation, we developed a high-affinity monoclonal antibody that specifically recognizes both apoA1 and HDL that have been modified by the MPO-H2O2-Cl− system. An oxindolyl alanine (2-OH-Trp) moiety at Trp72 of apoA1 is the immunogenic epitope. Mutagenesis studies confirmed a critical role for apoA1 Trp72 in MPO-mediated inhibition of the ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol acceptor activity of apoA1 in vitro and in vivo. ApoA1 containing a 2-OH-Trp72 group (oxTrp72-apoA1) is in low abundance within the circulation but accounts for 20% of the apoA1 in atherosclerosis-laden arteries. OxTrp72-apoA1 recovered from human atheroma or plasma is lipid poor, virtually devoid of cholesterol acceptor activity and demonstrated both a potent proinflammatory activity on endothelial cells and an impaired HDL biogenesis activity in vivo. Elevated oxTrp72-apoA1 levels in subjects presenting to a cardiology clinic (n = 627) were associated with increased cardiovascular disease risk. Circulating oxTrp72-apoA1 levels may serve as a way to monitor a proatherogenic process in the artery wall.

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Metadata

Authors
Huang, Y., DiDonato, J. A., Levison, B. S., Schmitt, D., Li, L., Wu, Y., Buffa, J., Kim, T., Gerstenecker, G. S., Gu, X., Kadiyala, C. S., Wang, Z., Culley, M. K., Hazen, J. E., DiDonato, A. J., Fu, X., Berisha, S. Z., Peng, D., Nguyen, T. T., Liang, S., Chuang, C.-C., Cho, L., Plow, E. F., Fox, P. L., Gogonea, V., Tang, W. H. W., Parks, J. S., Fisher, E. A., Smith, J. D., & Hazen, S. L.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2014-01-26
Volume
20
Issue
2
Pages
193-203
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.3459
OpenAlex
W2010686434
Cited by
364
References
64
FWCI
47.19
Type
journal article
Language
en
Open access
green

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