4.6 Article

Detection of coronary atherosclerotic plaques with superficial proteoglycans and foam cells using real-time intrinsic fluorescence spectroscopy

Journal

ATHEROSCLEROSIS
Volume 215, Issue 1, Pages 96-102

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2010.11.020

Keywords

Tryptophan; Low-density lipoprotein; Versican; Foam cells; Spectroscopy

Funding

  1. Pfizer, Inc.
  2. MIT Laser Biomedical Research Center
  3. National Institutes of Health [RR02594, R01 HL64675]

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Objectives: The protein components of low-density lipoprotein (LDL), oxidized LDL and proteoglycans such as versican contain tryptophan, an amino acid with characteristic fluorescence features at 308nm excitation wavelength. We hypothesize that intrinsic fluorescence spectroscopy at 308nm excitation wavelength (IFS(308)), a method suitable for clinical use, can identify coronary artery lesions with superficial foam cells (SFCs) and/or proteoglycans. Methods: We subjected 119 human coronary artery specimens to in vitro fluorescence and reflectance spectroscopy. We used 5 basis spectra to model IFS308, and extracted their contributions to each individual IFS308 spectrum. A diagnostic algorithm using the contributions of Total Tryptophan and fibrous cap to IFS308 was built to identify specimens with SFCs and/or proteoglycans in their top 50 mu m. Results: We detected SFCs and/or proteoglycans, such as versican or the glycosaminoglycan hyaluronan, in 24 fibrous cap atheromas or pathologic intimal thickening (PIT) lesions. An algorithm using the contributions of Total Tryptophan and fibrous cap to IFS308 was able to identify these segments with 92% sensitivity and 80% specificity. Conclusion: We were able to establish a set of characteristic LDL, oxidized LDL, versican and hyaluronan fluorescence spectra, ready to be used for real-time diagnosis. The IFS308 technique detects SFCs and/or proteoglycans in fibrous cap atheromas and PIT lesions. SFCs and proteoglycans are histological markers of vulnerable plaques, and this study is a step further in developing an invasive clinical tool to detect the vulnerable atherosclerotic plaque. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

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