The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development
Open accessAbstract
Increased lipoprotein-associated phospholipase A2 (Lp-PLA2) activity is associated with increased risk of cardiac events, but it is not known whether Lp-PLA2 is a causative agent. Here we show that selective inhibition of Lp-PLA2 with darapladib reduced development of advanced coronary atherosclerosis in diabetic and hypercholesterolemic swine. Darapladib markedly inhibited plasma and lesion Lp-PLA2 activity and reduced lesion lysophosphatidylcholine content. Analysis of coronary gene expression showed that darapladib exerted a general anti-inflammatory action, substantially reducing the expression of 24 genes associated with macrophage and T lymphocyte functioning. Darapladib treatment resulted in a considerable decrease in plaque area and, notably, a markedly reduced necrotic core area and reduced medial destruction, resulting in fewer lesions with an unstable phenotype. These data show that selective inhibition of Lp-PLA2 inhibits progression to advanced coronary atherosclerotic lesions and confirms a crucial role of vascular inflammation independent from hypercholesterolemia in the development of lesions implicated in the pathogenesis of myocardial infarction and stroke.
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Cites
Atherosclerosis--an inflammatory disease
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Cited by
Atherosclerosis: current pathogenesis and therapeutic options
Weber, C., & Noels, H. (2011) · Nature Medicine · doi:10.1038/nm.2538 · Cited by 2,203
Phospholipase A2 structure/function, mechanism, and signaling
Burke, J. E., & Dennis, E. A. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r800033-jlr200 · Cited by 933
An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases
Law, S.-H., Chan, M.-L., Marathe, G. K., Parveen, F., Chen, C.-H., & Ke, L.-Y. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20051149 · Cited by 817
Genetics of coronary artery disease: discovery, biology and clinical translation
Khera, A. V., & Kathiresan, S. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2016.160 · Cited by 659
Darapladib for Preventing Ischemic Events in Stable Coronary Heart Disease
The STABILITY Investigators (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1315878 · Cited by 579
Metadata
- Authors
- Wilensky, R. L., Shi, Y., Mohler, E. R., Hamamdzic, D., Burgert, M. E., Li, J., Postle, A., Fenning, R. S., Bollinger, J. G., Hoffman, B. E., Pelchovitz, D. J., Yang, J., Mirabile, R. C., Webb, C. L., Zhang, L., Zhang, P., Gelb, M. H., Walker, M. C., Zalewski, A., & Macphee, C. H.
- Venue
- Nature Medicine
- Published
- 2008-09-21
- Volume
- 14
- Issue
- 10
- Pages
- 1059-1066
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2099917925
- Cited by
- 387
- References
- 5
- FWCI
- 13.32
- Type
- journal article
- Language
- en
- Open access
- green
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- Wilensky, R. L., Shi, Y., Mohler, E. R., Hamamdzic, D., Burgert, M. E., Li, J., Postle, A., Fenning, R. S., Bollinger, J. G., Hoffman, B. E., Pelchovitz, D. J., Yang, J., Mirabile, R. C., Webb, C. L., Zhang, L., Zhang, P., Gelb, M. H., Walker, M. C., Zalewski, A., & Macphee, C. H. (2008). Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development. Nature Medicine. https://doi.org/10.1038/nm.1870
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
