Interaction of lipoprotein(a) with fibronectin and its potential role in atherogenesis.
The plasma concentration of lipoprotein (a) (Lp(a] varies widely in humans, and elevated concentrations of this lipoprotein are correlated with progression of atherosclerosis. Structural studies of Lp(a) have revealed that it is a low density lipoprotein (LDL)-like particle containing a unique glycoprotein, apo(a), which shares extensive homology with plasminogen. The apo(a) portion of Lp(a) binds to the carboxy-terminal heparin-binding domain of fibronectin. Incubation of Lp(a) or isolated apo(a) with fibronectin results in proteolytic cleavage of fibronectin which is, as visualized by gel electrophoresis and immunoblotting, distinct from that caused by plasmin or kallikrein. The proteolytic activity of apo(a) is of serine proteinase-type and displays specificity for arginine rather than lysine bonds. The molecular mechanism(s) underlying the association between Lp(a) and atherosclerosis remains an enigma.
Ehnholm
C
C
National Public Health Institute, Helsinki, Finland.
Jauhiainen
M
M
Metso
J
J
D000595:Amino Acid Sequence; D001161:Arteriosclerosis / Q000503:physiopathology*; D005353:Fibronectins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data
D005353:Fibronectins; D017270:Lipoprotein(a); D008074:Lipoproteins