The apolipoprotein(a) component of lipoprotein(a) mediates binding to laminin:contribution to selective retention of lipoprotein(a) in atherosclerotic lesions.

Lipoprotein(a) [Lp(a)] entrapment by vascular extracellular matrix may be important in atherogenesis. We sought to determine whether
laminin, a major component of the basal membrane, may contribute to Lp(a) retention in the arterial wall. First, immunohistochemistry
experiments were performed to examine the relative distribution of Lp(a) and laminin in human carotid artery specimens. There was a high
degree of co-localization of Lp(a) and laminin in atherosclerotic specimens, but not in non-atherosclerotic sections. We then studied the
binding interaction between Lp(a) and laminin in vitro. ELISA experiments showed that native Lp(a) particles and 17K and 12K recombinant
apolipoprotein(a) [r-apo(a)] variants interacted strongly with laminin whereas LDL, apoB-100, and the truncated KIV6-P, KIV8-P, and KIV9-P
r-apo(a) variants did not. Overall, the ELISA data demonstrated that Lp(a) binding to laminin is mediated by apo(a) and a combination of the
lysine analogue q-aminocaproic acid and salt effectively decreases apo(a) binding to laminin. Secondary binding analyses with 125I-labeled rapo(
a) revealed equilibrium dissociation constants (Kd) of 180 and 360 nM for the 17K and 12K variants binding to laminin, respectively.
Such similar Kd values between these two r-apo(a) variants suggest that isoform size does not appear to influence apo(a) binding to laminin.
In summary, our data suggest that laminin may bind to apo(a) in the atherosclerotic intima, thus contributing to the selective retention of
Lp(a) in this milieu.