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 KIV(6-P), KIV(8-P), and KIV(9-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 epsilon-aminocaproic acid and salt effectively decreases apo(a) binding to laminin. Secondary binding analyses with 125I-labeled r-apo(a) revealed equilibrium dissociation constants (K(d)) of 180 and 360 nM for the 17K and 12K variants binding to laminin, respectively. Such similar K(d) 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.
D'Angelo
Angela
A
Molecular Medicine Laboratory, University of Pavia, IRCCS Policlinico San Matteo, Piazzale Golgi 2, Pavia, Italy.
Geroldi
Diego
D
Hancock
Mark A
MA
Valtulina
Viviana
V
Cornaglia
Antonia I
AI
Spencer
Craig A
CA
Emanuele
Enzo
E
Calligaro
Alberto
A
Koschinsky
Marlys L
ML
Speziale
Pietro
P
Visai
Livia
L
D000818:Animals; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism*; D053241:Apoprotein(a); D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology*; D002339:Carotid Arteries / Q000033:anatomy & histology / Q000473:pathology; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D018082:Kringles; D007797:Laminin / Q000378:metabolism*; D017270:Lipoprotein(a) / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D011869:Radioligand Assay; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D001053:Apolipoproteins; D007797:Laminin; D017270:Lipoprotein(a); D011994:Recombinant Proteins; D053241:Apoprotein(a)