title: Molecular anatomy of ascending aorta in atherosclerosis by MS Imaging: Specific lipid and protein patterns reflect pathology.
abstract: 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.
authors.affiliation: Department of Immunology, IIS-Fundación Jiménez Díaz, UAM, REDinREN, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Martin-Lorenzo
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Balluff
authors.affiliation: Department of Immunology, IIS-Fundación Jiménez Díaz, UAM, REDinREN, Madrid, Spain.
authors.forename: Aroa S
authors.initials: AS
authors.lastname: Maroto
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Carreira
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rene J M
authors.initials: RJ
authors.lastname: van Zeijl
authors.affiliation: Department of Immunology, IIS-Fundación Jiménez Díaz, UAM, REDinREN, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Gonzalez-Calero
authors.affiliation: Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos, SESCAM, Toledo, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: de la Cuesta
authors.affiliation: Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos, SESCAM, Toledo, Spain.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Barderas
authors.affiliation: Department of Cardiac Surgery, Hospital Virgen de la Salud, SESCAM, Toledo, Spain.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Lopez-Almodovar
authors.affiliation: Department of Cardiology, Hospital Virgen de la Salud, SESCAM, Toledo, Spain.
authors.forename: Luis R
authors.initials: LR
authors.lastname: Padial
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: L.A.Mcdonnell@lumc.nl.
authors.forename: Liam A
authors.initials: LA
authors.lastname: McDonnell
authors.affiliation: Department of Immunology, IIS-Fundación Jiménez Díaz, UAM, REDinREN, Madrid, Spain; Department of Biochemistry and Molecular Biology I, Universidad Complutense, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Vivanco
authors.affiliation: Department of Immunology, IIS-Fundación Jiménez Díaz, UAM, REDinREN, Madrid, Spain. Electronic address: galvarez@fjd.es.
authors.forename: Gloria
authors.initials: G
authors.lastname: Alvarez-Llamas
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008055:Lipids; D013058:Mass Spectrometry; D011817:Rabbits; D013947:Thymosin / Q000378:metabolism*; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D061205:Vascular Calcification / Q000378:metabolism / Q000473:pathology; D000099201:Thymosin beta(4)
chemical_list: D008055:Lipids; D013947:Thymosin; D000099201:Thymosin beta(4)
keywords: Atherosclerosis; MALDI-MSI; Molecular imaging; Proteomics; Thymosin β4