Lipoprotein (a): Structure, Pathophysiology and Clinical Implications

Abstract

The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.

Arterial hypertension, obesity and non-alcoholic fatty liver disease: is there any connection?

“…Prognostic value of a significant increase in LP(a) in serum, as an important predictor of CV events, was confirmed in the studies that included patients with dyslipidaemia, hypertension, diabetes, the history of CV disease and non-alcoholic hepatic steatosis (NAHS) [38,72,73]. In parallel, the role of LP(a) as a genetic risk factor for CV disease was explained.…”

Exome sequencing identifies novel ApoB loss-of-function mutations causing hypobetalipoproteinemia in type 1 diabetes

“…Chylomicrons and low-density lipoprotein (LDL) are lipoprotein particles that consist mainly of TAGs and cholesterols, respectively [1][2][3][4]. Apolipoprotein B (ApoB), as the main apolipoprotein on chylomicrons and LDL, plays a pivotal role in the metabolism of lipids, especially TAGs and cholesterols.…”

Chemical composition of circulating native and desialylated low density lipoprotein: what is the difference?

“…For instance, Lp(a) level increased within 24 h after acute myocardial infarction, and its transient increase accompanied acute and chronic inflammatory processes. [29,30] Lp(a) gene polymorphism was associated with the incidence of cerebral vascular accident of large vessels, peripheral arterial disease, and abdominal aorta aneurysm. Lp(a) level also correlated with IL-6, tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), and monocyte chemoattractant protein (MCP-1) levels.…”