Functional approach to investigate Lp(a) in ischaemic heart and cerebral diseases.
BACKGROUND
Lp(a), a major cardiovascular risk factor, contains a specific apolipoprotein, apo(a), which by virtue of structural homology with plasminogen inhibits the formation of plasmin, the fibrinolytic enzyme. A number of clinical reports support the role of Lp(a) as a cardiovascular or cerebral risk factor, and experimental data suggest that it may contribute to atherothrombosis by inhibiting fibrinolysis.


METHODS
A well-characterized model of a fibrin surface and an apo(a)-specific monoclonal antibody were used to develop a functional approach to detect pathogenic Lp(a). The assay is based on the competitive binding of Lp(a) and plasminogen for fibrin, and quantifies fibrin-bound Lp(a). High Lp(a) binding to fibrin is correlated with decreased plasmin formation. In a transversal case-control study we studied 248 individuals: 105 had a history of ischaemic cardiopathy (IC), 52 had cerebro-vascular disease (CVD) of thrombotic origin, and 91 were controls.


RESULTS
The remarkably high apo(a) fibrin-binding in CVD (0.268 +/- 0.15 nmol L-1) compared with IC (0.155 +/- 0.12 nmol L-1) suggests the existence of peculiar and poorly understood differences in pro- or anti-thrombotic mechanisms in either cerebral and/or coronary arteries.


CONCLUSIONS
Our results demonstrated that Lp(a) fibrin-binding and small Apo(a) isoforms are associated with athero-thrombotic disease.
de la Peña-Díaz
A
A
Instituto Nacional de Cardiología Ignacio Chávez, México.
Cardoso-Saldaña
G
G
Zamora-González
J
J
Barinagarrementeria
F
F
Izaguirre
R
R
Loyau
S
S
Anglés-Cano
E
E
D000328:Adult; D001054:Apolipoproteins A / Q000097:blood; D001667:Binding, Competitive; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002561:Cerebrovascular Disorders / Q000097:blood*; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005341:Fibrinolysin / Q000096:biosynthesis; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood*; D010958:Plasminogen / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000097:blood
D001054:Apolipoproteins A; D015415:Biomarkers; D017270:Lipoprotein(a); D020033:Protein Isoforms; D005337:Fibrin; D010958:Plasminogen; D005341:Fibrinolysin