Protease imaging of human atheromata captures molecular information of atherosclerosis, complementing anatomic imaging

Dong Eog Kim, Jeong Yeon Kim, Dawid Schellingerhout, Eo Jin Kim, Hyang Kyoung Kim, Seulki Lee, Kwangmeyung Kim, Ick Chan Kwon, Soo Min Shon, Sang Wuk Jeong, So Hyang Im, Dong Kun Lee, Myoung Mook Lee, Geun Eun Kim

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Objective-There is hope that molecular imaging can identify vulnerable atherosclerotic plaques. However, there is a paucity of clinical translational data to guide the future development of this field. Here, we cross-correlate cathepsin-B or matrix metalloproteinase-2/-9 molecular optical imaging data of human atheromata or emboli with conventional imaging data, clinical data, and histopathologic data. Methods and Results-Fifty-two patients undergoing carotid endarterectomy (41 atheromata) or carotid stenting (15 captured emboli) were studied with protease-activatable imaging probes. We show that protease-related fluorescent signal in carotid atheromata or in emboli closely reflects the pathophysiologic alterations of plaque inflammation and statin-mediated therapeutic effects on plaque inflammation. Inflammation-related fluorescent signal was observed in the carotid bifurcation area and around ulcero-hemorrhagic lesions. Pathologically proven unstable plaques had high cathepsin-B-related fluorescent signal. The distribution patterns of the mean cathepsin-B imaging signals showed a difference between the symptomatic vs asymptomatic plaque groups. However, the degree of carotid stenosis or ultrasonographic echodensity was weakly correlated with the inflammatory proteolytic enzyme-related signal, suggesting that molecular imaging yields complimentary new information not available to conventional imaging. Conclusion-These results could justify and facilitate clinical trials to evaluate the use of protease-sensing molecular optical imaging in human atherosclerosis patients.

Original languageEnglish
Pages (from-to)449-456
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume30
Issue number3
DOIs
Publication statusPublished - 2010 Mar

Keywords

  • Atherosclerosis
  • Cathepsin-B
  • Molecular imaging
  • Protease
  • Structural imaging

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Kim, D. E., Kim, J. Y., Schellingerhout, D., Kim, E. J., Kim, H. K., Lee, S., Kim, K., Kwon, I. C., Shon, S. M., Jeong, S. W., Im, S. H., Lee, D. K., Lee, M. M., & Kim, G. E. (2010). Protease imaging of human atheromata captures molecular information of atherosclerosis, complementing anatomic imaging. Arteriosclerosis, thrombosis, and vascular biology, 30(3), 449-456. https://doi.org/10.1161/ATVBAHA.109.194613