Lipoprotein(a): Bedeutung für das fibrinolytische System und thromboembolische Komplikationen

Abstract

Lipoprotein(a) has been pre-occupying cardiovascular scientists since 1963. The pathogenic significance of the lipoprotein(a) molecule (Figure 1) with regard to the development of arteriosclerosis and coronary heart disease gained increasing recognition during the 1970s, as has its negative influence on the endothelial fibrinolytic system over the past 15 years. Although the importance of lipoprotein(a) for the fibrinolytic system has not been adequately assessed hitherto in the majority of cardiologic studies, it is, in fact, precisely this negative influence, that constitutes the actual risk for thrombotic complications in the cardiovascular system as a whole. However, the true risk factor seems to be a low isoform of apo(a). These patient groups, who can nowadays be accurately defined by means of molecular biological studies, may possibly constitute an at-risk population that can be protected from further thrombotic complications. This article sets out to examine the copious evidence for further proatherogenic and prothrombotic properties of lipoprotein(a) (Figure 2) and discuss the molecular and pathophysiological mechanisms in the critical stage in early atherogenesis and thrombosis.

Lipoprotein(a) - Structure, Epidemiology, Function and Diagnostics of a Cardiovascular Risk Marker

“…Now further investigation results allow the conclusion that apart from its significance as an important agent in the development of atherosclerosis, Lp(a) has even more physiological functions, e.g. in wound healing, angiogenesis and hemostasis [2,40,58]. In the context of pleiotropic actions, however, the favourable action mechanisms are opposed by pathogenetic mechanisms, whereby the importance of Lp(a) in atherogenesis should be particularly mentioned ( …”

“…Individual investigations indicate a possible favourable role of Lp(a) in wound healing [39,58]. After tissue lesions Lp(a) plasma concentrations may increase as a consequence of an acute phase reaction [2,39,58], then it comes to an accumulation of Lp(a) at the lesion and subsequently to a proliferation of smooth vascular muscle cells and endothelial cells and to a release of cholesterol into the tissue [58][59][60].…”

“…After tissue lesions Lp(a) plasma concentrations may increase as a consequence of an acute phase reaction [2,39,58], then it comes to an accumulation of Lp(a) at the lesion and subsequently to a proliferation of smooth vascular muscle cells and endothelial cells and to a release of cholesterol into the tissue [58][59][60]. This led to the theory that a few million years ago, when plasma cholesterol concentrations were assumed to be much lower, Lp(a) could have been a substantial source for the supply of tissues with cholesterol which was to be used in tissue regeneration and repair.…”

“…This led to the theory that a few million years ago, when plasma cholesterol concentrations were assumed to be much lower, Lp(a) could have been a substantial source for the supply of tissues with cholesterol which was to be used in tissue regeneration and repair. This would have been an evolutionary advantage, which later transformed into a risk factor due to altered circumstances [39,58].…”

“…During fibrinolysis, physiological importance of which lies in the dissolution of fibrin deposits and in the restoration of an injured vascular endothelium [68], the binding of plasminogen to lysine residues results in plasmin activation and subsequently in the enhancement of the following fibrinolytic processes [69][70][71][72][73][74]. Lp(a) binding also involves lysine [65] with the consequence, that due to the lack of catalytic activity it comes to hypofibrinolysis and, due to the LDL-component of the Lp(a), to an accumulation of cholesterol [2,40,41,58,65,[75][76][77]. Moreover, Lp(a) stimulates the synthesis of plasminogen activator-inhibitor I (PAI-I) in endothelial cells or of PAI-II in monocytes [2,78].…”