TY - JOUR
T1 - Molecular anatomy of ascending aorta in atherosclerosis by MS Imaging
T2 - Specific lipid and protein patterns reflect pathology
AU - Martin-Lorenzo, Marta
AU - Balluff, Benjamin
AU - Maroto, Aroa S
AU - Carreira, Ricardo J
AU - van Zeijl, Rene J M
AU - Gonzalez-Calero, Laura
AU - de la Cuesta, Fernando
AU - Barderas, Maria G
AU - Lopez-Almodovar, Luis F
AU - Padial, Luis R
AU - McDonnell, Liam A
AU - Vivanco, Fernando
AU - Alvarez-Llamas, Gloria
N1 - Copyright © 2015 Elsevier B.V. All rights reserved.
PY - 2015/8/3
Y1 - 2015/8/3
N2 - The molecular anatomy of healthy and atherosclerotic tissue is pursued here to identify ongoing molecular changes in atherosclerosis development. Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. Mass spectrometry imaging (MSI) is a novel unexplored ex vivo imaging approach in CVD able to provide in-tissue molecular maps. A rabbit model of early atherosclerosis was developed and high-spatial-resolution MALDI-MSI was applied to comparatively analyze histologically-based arterial regions of interest from control and early atherosclerotic aortas. Specific protocols were applied to identify lipids and proteins significantly altered in response to atherosclerosis. Observed protein alterations were confirmed by immunohistochemistry in rabbit tissue, and additionally in human aortas. Molecular features specifically defining different arterial regions were identified. Localized in the intima, increased expression of SFA and lysolipids and intimal spatial organization showing accumulation of PI, PG and SM point to endothelial dysfunction and triggered inflammatory response. TG, PA, SM and PE-Cer were identified specifically located in calcified regions. Thymosin β4 (TMSB4X) protein was upregulated in intima versus media layer and also in response to atherosclerosis. This overexpression and localization was confirmed in human aortas. In conclusion, molecular histology by MS Imaging identifies spatial organization of arterial tissue in response to atherosclerosis.
AB - The molecular anatomy of healthy and atherosclerotic tissue is pursued here to identify ongoing molecular changes in atherosclerosis development. Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. Mass spectrometry imaging (MSI) is a novel unexplored ex vivo imaging approach in CVD able to provide in-tissue molecular maps. A rabbit model of early atherosclerosis was developed and high-spatial-resolution MALDI-MSI was applied to comparatively analyze histologically-based arterial regions of interest from control and early atherosclerotic aortas. Specific protocols were applied to identify lipids and proteins significantly altered in response to atherosclerosis. Observed protein alterations were confirmed by immunohistochemistry in rabbit tissue, and additionally in human aortas. Molecular features specifically defining different arterial regions were identified. Localized in the intima, increased expression of SFA and lysolipids and intimal spatial organization showing accumulation of PI, PG and SM point to endothelial dysfunction and triggered inflammatory response. TG, PA, SM and PE-Cer were identified specifically located in calcified regions. Thymosin β4 (TMSB4X) protein was upregulated in intima versus media layer and also in response to atherosclerosis. This overexpression and localization was confirmed in human aortas. In conclusion, molecular histology by MS Imaging identifies spatial organization of arterial tissue in response to atherosclerosis.
U2 - 10.1016/j.jprot.2015.06.005
DO - 10.1016/j.jprot.2015.06.005
M3 - Article
C2 - 26079611
VL - 126
SP - 245
EP - 251
JO - Journal of proteomics
JF - Journal of proteomics
SN - 1874-3919
ER -