Lipoprotein(a) isoforms display differences in affinity for plasminogen-like binding to human mononuclear cells

Area of Science:

• Biochemistry
• Cardiovascular Science
• Molecular Biology

Background:

• Lipoprotein(a) (Lp(a)) binding to monocyte-macrophage membrane proteins is implicated in atheroma formation.
• Distinct apolipoprotein(a) (apo(a)) isoforms may exhibit varying affinities for fibrin, suggesting potential differences in cellular interactions.

Purpose of the Study:

• To investigate the functional behavior of apo(a) isoforms within Lp(a) during interaction with monocytic cells.
• To explore whether apo(a) isoform size influences binding affinity to THP-1 cells and fibrin surfaces.

Main Methods:

• Purification of Lp(a) with small and high molecular mass apo(a) isoforms from patient plasma.
• Radioisotopic dilution assays to measure the binding of Lp(a) and plasminogen to THP-1 cells.
• Langmuir equation analysis to determine binding affinity (Kd) and site characteristics.
• Assessment of Lp(a) binding to a fibrin surface.

Main Results:

• Small apo(a) isoforms demonstrated high-affinity binding to THP-1 cells (Kd = 25.8 ± 19 nmol/L), significantly higher than plasminogen.
• Small apo(a) isoforms also showed higher affinity for fibrin (Kd = 17.5 ± 7.9 nmol/L) compared to plasminogen.
• High molecular mass apo(a) isoforms exhibited lower affinity and did not show saturation at tested concentrations.

Conclusions:

• Apolipoprotein(a) isoforms display functional heterogeneity in binding to cells and fibrin, linked to their size.
• The higher affinity of small apo(a) isoforms for cells and fibrin may contribute to their association with increased cardiovascular risk.
• Qualitative differences in apo(a) isoform binding could modulate the cardiovascular risk associated with elevated Lp(a) levels.