Raman microspectroscopy and Raman imaging reveal biomarkers specific for thoracic aortic aneurysms

Kaori Sugiyama; Julia Marzi; Julia Alber; Eva M Brauchle; Masahiro Ando; Yoshito Yamashiro; Bhama Ramkhelawon; Katja Schenke-Layland; Hiromi Yanagisawa

doi:10.1016/j.xcrm.2021.100261

Raman microspectroscopy and Raman imaging reveal biomarkers specific for thoracic aortic aneurysms

Cell Rep Med. 2021 Apr 28;2(5):100261. doi: 10.1016/j.xcrm.2021.100261. eCollection 2021 May 18.

Authors

Kaori Sugiyama^{1

2}, Julia Marzi^{3

4

5}, Julia Alber³, Eva M Brauchle^{3

4

5}, Masahiro Ando^{6

7}, Yoshito Yamashiro¹, Bhama Ramkhelawon⁸, Katja Schenke-Layland^{3

4

5

9}, Hiromi Yanagisawa^{1

10}

Affiliations

¹ Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Japan.
² Institute for Advanced Research of Biosystem Dynamics, Research Institute for Science and Engineering, Waseda University, Tokyo, Japan.
³ Department of Women's Health, Research Institute of Women's Health, Eberhard Karls University, Tübingen, Germany.
⁴ NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.
⁵ Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies," University of Tübingen, Tübingen, Germany.
⁶ Research Organization for Nano & Life Innovation, Waseda University, Tokyo, Japan.
⁷ Japan Science and Technology Agency, PRESTO, Saitama, Japan.
⁸ Division of Vascular Surgery, Department of Surgery and Department of Cell Biology, New York University Langone Health, New York, NY, USA.
⁹ Department of Medicine/Cardiology, Cardiovascular Research Laboratories, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
¹⁰ Department of Basic Medical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Abstract

Aortic rupture and dissection are life-threatening complications of ascending thoracic aortic aneurysms (aTAAs), and risk assessment has been largely based on the monitoring of lumen size enlargement. Temporal changes in the extracellular matrix (ECM), which has a critical impact on aortic remodeling, are not routinely evaluated, and cardiovascular biomarkers do not exist to predict aTAA formation. Here, Raman microspectroscopy and Raman imaging are used to identify spectral biomarkers specific for aTAAs in mice and humans by multivariate data analysis (MVA). Multivariate curve resolution-alternating least-squares (MCR-ALS) combined with Lasso regression reveals elastic fiber-derived (Ce1) and collagen fiber-derived (Cc6) components that are significantly increased in aTAA lesions of murine and human aortic tissues. In particular, Cc6 detects changes in amino acid residues, including phenylalanine, tyrosine, tryptophan, cysteine, aspartate, and glutamate. Ce1 and Cc6 may serve as diagnostic Raman biomarkers that detect alterations of amino acids derived from aneurysm lesions.

Keywords: Raman imaging; ascending thoracic aortic aneurysm; biomarkers; collagens; elastic fibers; extracellular matrix; mouse model; multivariate data analysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Aorta / pathology
Aorta, Thoracic / pathology*
Aortic Aneurysm / pathology*
Aortic Aneurysm, Thoracic / pathology*
Aortic Dissection / pathology
Aortic Rupture / pathology
Biomarkers / analysis*
Humans
Mice
Spectrum Analysis, Raman* / methods
Stress, Mechanical
Tensile Strength / physiology

Substances

Biomarkers