Lipoprotein(a) and the link between atherosclerosis and thrombosis.
Elevated plasma concentrations of lipoprotein(a) (Lp[a]) have been consistently shown to be a risk factor for the development of a variety of thrombotic and atherosclerotic disorders including coronary artery disease. However, the mechanisms by which Lp(a) mediates its apparent pathophysiological effects remain to be conclusively determined. Atherosclerosis and thrombosis are functionally linked because it is thrombotic events, which ensue most often from the rupture of an unstable atherosclerotic plaque, that are the most significant manifestations of atherosclerotic disease. Lp(a) is a candidate to directly mediate this functional linkage in that this lipoprotein is capable of both proatherogenic and prothrombotic effects. In addition, Lp(a) has a profound effect on endothelial function, perturbation of which has important ramifications for both atherogenesis and thrombosis. Indeed, Lp(a) is capable of deleteriously altering the balance between the pro- and anticoagulant, pro- and anti-inflammatory, and vasorelaxing and vasoconstricting properties of the endothelium. In addition, Lp(a) is capable of perturbing the barrier function of the endothelium. As such, Lp(a) constitutes a functional link not only between atherosclerosis and thrombosis, but also between endothelial dysfunction and both of these disease processes.
Department of Biochemistry, Queen's University, Kingston, Ontario. mk11@post.queensu.ca
Marlys L
ML
Koschinsky
D000818:Animals; D050197:Atherosclerosis / Q000401:mortality / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000401:mortality / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D000882:Haplorhini; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood / Q000378:metabolism*; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016019:Survival Analysis; D020246:Venous Thrombosis / Q000401:mortality / Q000503:physiopathology*
D015415:Biomarkers; D017270:Lipoprotein(a)