Lipoprotein(a) and its role in inflammation, atherosclerosis and malignancies

Abstract

Lipoprotein (a) (Lp(a)) is a modified low-density lipoprotein (LDL) particle with an additional specific apolipoprotein (a), covalently attached to apolipoprotein B‑100 of LDL by a single thioester bond. Increased plasma Lp(a) level is a genetically determined, independent, causal risk factor for cardiovascular disease.The precise quantification of Lp(a) in plasma is still hampered by mass-sensitive assays, large particle variation, poor standardization and lack of assay comparability.The physiological functions of Lp(a) include wound healing, promoting tissue repair and vascular remodeling. Similarly to other lipoproteins, Lp(a) is also susceptible for oxidative modifications, leading to extensive formation of pro-inflammatory and pro-atherogenic oxidized phospholipids, oxysterols, oxidized lipid-protein adducts in Lp(a) particles, that perpetuate atherosclerotic lesion progression and intima-media thickening through induction of M1-macrophages, inflammation, autoimmunity and apoptosis. The oxidation-specific epitopes of modified lipoproteins are major targets of pre-immune, natural IgM antibodies, that may attenuate the pro-inflammatory and pro-atherogenic effects of Lp(a).Although the data are still insufficient, recent studies suggest a potential anti-neoplastic role of Lp(a).

Correlation between serum low-density lipoprotein cholesterol concentration and arterial wall stiffness

“…www.kardiologiapolska.pl Data are presented as mean ± standard deviation or number (percentage). BMI -body mass index; C1 -large-artery elasticity index; C2small-artery elasticity index; DBP -diastolic blood pressure; HDL-C -high-density lipoprotein cholesterol; LDL-C -low-density lipoprotein cholesterol; SBP -systolic blood pressure Serum LDL-C concentration -0.18 -0.13 to -0.23 < 0.01 CI -confidence interval; other abbreviations -see Table 1 www.kardiologiapolska.pl The results of our research partially coincide with those obtained by Schillinger et al [13], who showed an association between high serum concentrations of lipoprotein(a) (a modified LDL particle with strong pro-inflammatory and pro-atherogenic effects [14]) and reduced compliance of the small artery walls. In a group of subjects with atherosclerosis, the observed negative correlation between serum lipoprotein(a) and C2 was independent of other risk factors such as sex, smoking status, and diabetes.…”

Lipoprotein apheresis is an optimal therapeutic option to reduce increased Lp(a) levels

“…Many connections between the immune system and metabolism exist; acute inflammation induces hypertriglyceridemia [26], whereas chronic inflammation in the arterial walls has more complex effects, like in rheumatoid arthritis [27]. Novel approaches such as anti-inflammatory therapies like the CAN-TOS trial [13,14], T-cell-based treatments or vaccination against LDL or Lp(a) [28] could potentially reduce cardiovascular inflammation and protect against the development of atherosclerosis [29][30][31]. In addition cell-cell communication is important to maintain the inflammatory settings [32].…”

Chronic inflammation and lipid profile parameters in obese subjects with normal and disturbed glucose metabolism

“…Convincing evidence has been presented that the proinflammatory and pro-atherosclerotic effects of Lp(a) are largely attributed to different oxidation-specific epitopes (produced in response to reactive oxygen species), present in Lp(a) particles [3]. This might explain a significant change in correlation levels before and after the metformin treatment.…”

“…Although this chronic stress does not cause reaction such strong as the acute inflammation does, it is still involved in a development of various degenerative diseases including diabetes and cardiovascular diseases (CVD). Lipoprotein (a) [Lp(a)] levels are associated with CVD, as Lp(a) may play a role in atherothrombosis and in activation of acute inflammation [3]. It is also involved in the activation of endothelial reaction, oxidative modification and formation of foam cells, processes involved in atherosclerosis progression [3,4].…”