The role of lipoprotein[a] in atherosclerosis.
Recent studies confirm and extend previous evidence that lipoprotein (Lp) plays a significant role in atherosclerosis and is one of the top five or six risk factors for cardiovascular disease. In Japanese patients, Lp levels and apo phenotypes are significant predictors for myocardial infarction. Lp levels are significantly higher in ischemic stroke patients than in controls. However, plasma concentrations of Lp are not predictive of ischemic cerebral infarction in either men or women. Serum Lp levels are significantly higher in patients with carotid plaques or measurable intima-media thickness than in controls without. Despite these associations, there is no significant relationship between Lp level and arterial endothelial function, smooth muscle response, or carotid wall thickness, even though other lipid risk factors like low-density lipoprotein cholesterol (LDL-C) and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio are correlated with abnormal arterial function and structure. There is new evidence that the association of Lp with extracellular matrix (ECM) secreted by arterial smooth muscle cells increases two- to threefold the subsequent specific binding of LDL. Alpha-defensins released from activated or senescent neutrophils stimulate the binding of Lp to ECM of endothelial cells. Several factors that affect the accumulation of Lp and oxidized LDL in the arterial intima have been identified. Several recent studies have provided new insights into the physiologic role that Lp might play in compromising fibrinolysis. The interaction of Lp with cells is clearly distinct from that with ECM and with fibrinogen; the regulation sites within Lp and plasminogen for these regulatory molecules are not identical. These recent advances bring us significantly closer to understanding how Lp exerts its atherogenic and thrombogenic properties.
Morrisett
J D
JD
Baylor College of Medicine, The Methodist Hospital, A601, 6565 Fannin Street, Houston, TX 77030, USA. morriset@bcm.tmc.edu
D001161:Arteriosclerosis / Q000097:blood* / Q000209:etiology / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood* / Q000235:genetics; D012307:Risk Factors
D015415:Biomarkers; D017270:Lipoprotein(a)