Apolipoprotein kinetics measured in human HDL by HR/AM-PRM unveils a novel picture of HDL metabolism.

摘要

ApoA-I is a marker for circulating high-density lipoprotein (HDL). The metabolism of apoA-I and other HDL apolipoproteins may lead to an improved understanding of HDL function in humans and eventually the development of reliable clinical markers of coronary heart disease. We present the first ever report of high-resolution/accurate-mass parallel reaction monitoring (HR/AM-PRM) to measure low-abundant D3-Leu tracer enrichment (0.03% to 1.0%), which is necessary to determine in vivo the kinetic parameters of apoA-I. Our intensity-based quantification method, accompanied with HR/AM-PRM, can separate 2H M3 ions (D3-Leu) from surrounding non-specific peaks, such as the natural M3 ion (Δm=12mDa), and produce accurate data points for multicompartmental modeling to identify the source, conversion, and removal pathways for apoA-I across the HDL size fractions.