Decoding Cardiovascular Disease Through Spatial Proteomics

Area of Science:

• Cardiovascular Biology
• Proteomics
• Spatial Biology

Background:

• Cardiovascular function relies on intricate tissue architectures, including cell and extracellular matrix organization.
• Spatial proteomics is crucial for understanding cardiovascular biology and disease by mapping protein distribution.
• Existing spatial proteomics methods vary in scope, from localized analysis to broad tissue mapping.

Purpose of the Study:

• To review spatial proteomics strategies applicable to cardiovascular research.
• To discuss the strengths and limitations of different spatial proteomics technologies.
• To propose an integrated workflow for comprehensive cardiovascular tissue analysis.

Main Methods:

• Categorization of spatial proteomics into region-of-interest (ROI)-based and tissue mapping approaches.
• Evaluation of technologies based on molecular depth, spatial coverage, and spatial resolution.
• Proposal of a sequential workflow combining untargeted tissue mapping with targeted ROI analysis.

Main Results:

• Neither tissue mapping nor ROI-based methods alone fully capture cardiovascular tissue complexity.
• An integrated approach leverages the complementary strengths of both mapping and ROI strategies.
• This integrated workflow provides multiscale insights into spatially organized cardiovascular disease processes.

Conclusions:

• Comprehensive understanding of cardiovascular tissue requires both broad spatial organization and localized molecular detail.
• An integrated workflow using untargeted mapping followed by targeted validation is proposed.
• This approach enhances mechanistic insights into cardiovascular biology and disease.