Lipoprotein(a): From Molecules to Therapeutics

Abstract

Lipoprotein (a) [Lp(a)] was discovered by Kare Berg in 1963 from the study of low-density lipoprotein genetic variants. Lp(a) contains a unique protein, apolipoprotein(a), which is linked to the Apo B-100 through a disulfide bond that gives it a great structural homology with plasminogen, and confers it atherogenic and atherothrombotic properties. Interest in Lp(a) has increased because an important association between high plasma levels of Lp(a) and coronary artery disease and cerebral vascular disorders has been demonstrated. Numerous case control studies have confirmed that hyper-Lp(a) is a risk factor for premature cardiovascular disease. Lp(a) is identified as a genetic trait with autosomal transmission, codified by one of the most studied polymorphic genes in humans. It has been demonstrated that variations in this gene are a major factor in the serum levels of Lp(a). Variations differ considerably between individuals and sex across populations. Various approaches to drug treatment using fibric acid derivatives, growth hormone, insulin-like growth factor-1, alcohol extracted soy protein, niacin, and exercise have been proven to decrease Lp(a) in high risk patients, but none has really been an effective therapeutic option for successfully reducing Lp(a) plasma levels.

Variations of Lipoprotein(a) Levels in the Metabolic Syndrome: A Report from the Maracaibo City Metabolic Syndrome Prevalence Study

“…Based on these premises, dyslipidemia, and inflammation, Lp(a) plays an important role at the molecular level both for CVD and MS when its plasmatic concentration is elevated, being able to generate both of the aforementioned basic disturbances [31–33]. However, research assessing its epidemiological behavior remains scarce.…”

Biomarker analysis of Morquio syndrome: identification of disease state and drug responsive markers

“…Elevated lipoprotein(a) levels are associated with an increased risk of atherosclerosis-related events such as cardiovascular disease and stroke. Lipoprotein(a) is believed to be involved in forming atherosclerotic plaques and enhancing platelet interaction [17]. It also correlates with inflammatory activity, as seen in patients with rheumatoid arthritis (RA) [18].…”

The Effects of Tamoxifen on Plasma Lipoprotein(a) Concentrations: Systematic Review and Meta-Analysis

“…Lipoprotein(a) [Lp(a)], first discovered by Kare Berg in 1963, is a low-density lipoprotein (LDL)-like particle containing apolipoprotein(a) [apo(a)] and apolipoprotein B-100 (apo-B100) linked through a disulfide bond [1]. It has been shown that Lp(a) contributes to atherosclerosis through accelerated transport of oxidized phospholipids [2] and inhibition of fibrinolysis [3].…”