Molecular anatomy of ascending aorta in atherosclerosis by MS Imaging: Specific lipid and protein patterns reflect pathology

• A novel unexplored ex vivo imaging approach in cardiovascular disease
• 30 μm high spatial resolution is applied here to atherosclerosis tissue.
• Specific protein/lipid patterns responding to atherosclerosis define arterial layers.
• TMSB4X up-regulation in atherosclerosis is firstly identified at its original location.

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.

Specific molecular patterns defining arterial layers in atherosclerosis.Figure optionsDownload high-quality image (155 K)Download as PowerPoint slide