Associations Between Plasma Lipoprotein(a) Levels and Circulating Monocyte Subsets Differ across Populations

Area of Science:

• Cardiovascular Research
• Immunology
• Genetics

Background:

• Lipoprotein(a) [Lp(a)] is a known cardiovascular disease (CVD) risk factor, with higher plasma concentrations typically observed in Black individuals compared to White individuals.
• Elevated Lp(a) and its associated oxidized phospholipids (oxPL) may promote arterial inflammation by influencing monocyte phenotypes.

Purpose of the Study:

• To investigate the associations between Lp(a) levels, apo(a) isoform size, and circulating monocyte populations in Black and White individuals.
• To explore the role of race in modifying these associations using single-cell RNA sequencing (scRNA-seq).

Main Methods:

• Plasma Lp(a), apo(a) isoform size, inflammatory markers, and oxPL were measured in a cohort of 34 participants (20 Black, 14 White) after exclusions.
• Multivariable linear regression and scRNA-seq were used to analyze associations between Lp(a), oxPL, and monocyte subset proportions.
• Participants were stratified into normal and high Lp(a) groups.

Main Results:

• Monocyte subset distributions did not significantly differ between normal and high Lp(a) groups.
• Race significantly modified the association between plasma Lp(a) levels and non-classical monocyte abundance, showing an inverse association in White participants but not in Black participants.
• OxPL bound to apo(a) correlated strongly with plasma Lp(a) and exhibited race-dependent associations with non-classical monocytes and classical 2 monocytes.

Conclusions:

• The relationship between Lp(a), oxPL, and circulating monocyte subsets is race-dependent.
• Self-reported race is an important consideration in research examining Lp(a)-related immune responses and cardiovascular phenotypes.