SECTM1 Regulates Monocyte Levels and Is Associated With Incident Coronary Heart Disease

Area of Science:

• Cardiovascular proteomics
• Biomarker discovery
• Monocyte biology

Background:

• Coronary heart disease (CHD) remains a leading cause of mortality worldwide.
• Identifying novel biomarkers and understanding underlying pathways are crucial for effective prevention and treatment.
• Proteomic profiling offers a powerful approach to uncover new biological insights into complex diseases like CHD.

Purpose of the Study:

• To identify novel protein biomarkers associated with incident coronary heart disease (CHD) using proteomic profiling.
• To investigate the functional role of identified biomarkers in the context of CHD pathogenesis.
• To validate findings in an independent cohort.

Main Methods:

• Proteomic profiling of approximately 1,300 proteins in 1,967 Black individuals from the Jackson Heart Study.
• Validation of top findings in the Cardiovascular Health Study cohort.
• Analysis of genetic variants associated with the top biomarker using a genomic database.
• In vivo studies using recombinant SECTM1a to assess its effect on monocyte populations.

Main Results:

• Secreted and Transmembrane Protein 1 (SECTM1), a monocyte chemoattractant, was identified as a novel protein significantly associated with incident CHD.
• The top genetic variant (rs116473040) linked to SECTM1 was associated with the percentage of circulating monocytes.
• In vivo experiments showed that SECTM1a administration increased the proportion of proatherogenic Ly6Chi monocytes.

Conclusions:

• SECTM1 is a novel potential biomarker for coronary heart disease.
• SECTM1 may contribute to CHD pathogenesis by modulating monocyte populations, specifically increasing proatherogenic monocytes.
• These findings highlight a potential therapeutic target for CHD prevention and treatment.