Lipoprotein(a) and atherosclerosis: new perspectives on the mechanism of action of an enigmatic lipoprotein.
Although elevated plasma concentrations of lipoprotein(a) (Lp(a)) have been identified as a risk factor for coronary heart disease, the pathophysiologic and physiologic roles of Lp(a) continue to elude basic researchers and clinicians alike. Lp(a) is a challenging lipoprotein to study because it has a complex structure consisting of a low-density lipoprotein-like moiety to which is covalently attached the unique glycoprotein apolipoprotein(a) (apo(a)). Apo(a) contains multiply repeated kringle domains that are similar to a sequence found in the fibrinolytic proenzyme plasminogen; differing numbers of kringle sequences in apo(a) give rise to Lp(a) isoform size heterogeneity. In addition to elevated plasma concentrations of Lp(a), apo(a) isoform size has been identified as a risk factor for coronary heart disease, although studies addressing this relationship have been limited. The similarity of Lp(a) to low-density lipoprotein and plasminogen provides an enticing link between the processes of atherosclerosis and thrombosis, although a clear demonstration of this association in vivo has not been provided. Clearly, Lp(a) is a risk factor for both atherothrombotic and purely thrombotic events; a plethora of mechanisms to explain these clinical findings has been provided by both in vitro studies as well as animal models for Lp(a).
Koschinsky
Marlys L
ML
Department of Biochemistry, Queen's University, A208 Botterell Hall, Kingston, ON K7L 3N6, Canada. mk11@post.queensu.ca
D000818:Animals; D003324:Coronary Artery Disease / Q000097:blood* / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood / Q000150:complications / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D017270:Lipoprotein(a) / Q000097:blood* / Q000737:chemistry / Q000187:drug effects; D012307:Risk Factors
D000960:Hypolipidemic Agents; D017270:Lipoprotein(a)