TY - JOUR
T1 - Raman microspectroscopy and Raman imaging reveal biomarkers specific for thoracic aortic aneurysms
AU - Sugiyama, Kaori
AU - Marzi, Julia
AU - Alber, Julia
AU - Brauchle, Eva M.
AU - Ando, Masahiro
AU - Yamashiro, Yoshito
AU - Ramkhelawon, Bhama
AU - Schenke-Layland, Katja
AU - Yanagisawa, Hiromi
N1 - Funding Information:
This work was supported in part by MEXT KAKENHI (grant nos. JP 17H04289 and JP 20H03762) and SENSHIN Medical Research Foundation, Japan, to H.Y. as well as the Deutsche Forschungsgemeinschaft (INST 2388/64-1 and Germany's Excellence Strategy, EXC 2180-390900677), the Ministry of Science, Research, and the Arts of Baden-Württemberg (33-729.55-3/214 and SI-BW 01222-91, to K.S.-L.), and the State Ministry of Baden-Württemberg for Economic Affairs, Labour and Housing Construction. M.A. was supported by JST, PRESTO (grant no. JPMJPR1671), Japan. The experiments were designed by K.S. K.S.-L. and H.Y. The Raman experiments were measured by K.S. J.A. (murine samples), and J.M. (human samples). The data analysis was executed by K.S. J.M. and M.A. TCA was analyzed by K.S. and J.M. PCA was mainly analyzed by J.M. MCR was mainly analyzed by K.S. and M.A. The murine samples were prepared by K.S. Y.Y. and H.Y. The human samples were provided by B.R. K.S. and J.M. wrote the manuscript, which was revised by E.M.B. M.A. K.S.-L. and H.Y. All of the authors commented on the paper. The authors declare no competing interests. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. It takes all kinds of minds to uncover new scientific discoveries.
Funding Information:
This work was supported in part by MEXT KAKENHI (grant nos. JP 17H04289 and JP 20H03762 ) and SENSHIN Medical Research Foundation , Japan, to H.Y., as well as the Deutsche Forschungsgemeinschaft ( INST 2388/64-1 and Germany’s Excellence Strategy , EXC 2180-390900677 ), the Ministry of Science, Research, and the Arts of Baden-Württemberg ( 33-729.55-3/214 and SI-BW 01222-91 , to K.S.-L.), and the State Ministry of Baden-Württemberg for Economic Affairs, Labour and Housing Construction . M.A. was supported by JST, PRESTO (grant no. JPMJPR1671 ), Japan.
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/5/18
Y1 - 2021/5/18
N2 - 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.
AB - 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.
KW - Raman imaging
KW - ascending thoracic aortic aneurysm
KW - biomarkers
KW - collagens
KW - elastic fibers
KW - extracellular matrix
KW - mouse model
KW - multivariate data analysis
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U2 - 10.1016/j.xcrm.2021.100261
DO - 10.1016/j.xcrm.2021.100261
M3 - Article
C2 - 34095874
AN - SCOPUS:85106243789
SN - 2666-3791
VL - 2
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 5
M1 - 100261
ER -