Spatial Metabolomics Identifies LPC(18:0) and LPA(18:1) in Advanced Atheroma With Translation to Plasma for...

Area of Science:

• Biochemistry
• Cardiovascular Biology
• Metabolomics

Background:

• Atherosclerosis pathogenesis involves poorly understood arterial metabolic alterations.
• Specific metabolic changes within arterial layers (plaque, media, adventitia) and cardiac tissue are largely unknown.
• Understanding these changes is crucial for assessing cardiovascular risk.

Purpose of the Study:

• To spatially resolve metabolic changes in murine aortas and adjacent cardiac tissue during atherosclerosis.
• To investigate the translatability of these findings to human atherosclerotic tissue and plasma for cardiovascular risk estimation.

Main Methods:

• Mass spectrometry imaging (MSI) applied to atherosclerotic and control murine aortas (n=11 each).
• Histology-guided virtual microdissection for region-specific analysis.
• MSI on human carotid arteries (n=9) and targeted mass spectrometry on human plasma (n=54) from coronary artery bypass grafting patients and controls.

Main Results:

• MSI revealed 362 local metabolic alterations in atherosclerotic mice.
• Altered glycerophospholipid metabolism observed in cardiac tissue and all aortic layers.
• Lysophosphatidylcholine (LPC(18:0)) and lysophosphatidic acid (LPA(18:1)) elevated in advanced plaques and human fibrotic areas.
• These lipids were reduced in human plasma of high-risk individuals, with LPC(18:0) showing significant cardiovascular risk association and diagnostic potential (AUC 0.778).

Conclusions:

• Atherosclerosis is associated with widespread phospholipid metabolism alterations in the aorta and heart.
• Tissue-identified plaque-progression lipids LPC(18:0) and LPA(18:1) are potential biomarkers for cardiovascular risk in human plasma.