Lipoprotein(a) and the atherothrombotic process: Mechanistic insights and clinical implications

Abstract

Although many epidemiologic studies have pointed at an association between plasma levels of lipoprotein(a) (Lp(a)) and cardiovascular risk, the data obtained have been conflicting because of a number of factors, particularly those dealing with plasma storage, lack of assay standardization, population sample size, age, gender, ethnic variations, and variable disease endpoints. Moreover, the attention has been primarily focused on whole Lp(a), with relatively less emphasis on its constituent apolipoprotein(a) and on the apolipoprotein B100-containing lipoprotein, mainly low-density lipoprotein (LDL), to which apolipoprotein(a) is linked. According to recent studies, small-size apolipoprotein(a) isoforms may represent a cardiovascular risk factor either by themselves or synergistically with plasma Lp(a) concentration. Moreover, the density properties of the LDL moiety may have an impact on Lp(a) pathogenicity. It has also become apparent that Lp(a) can be modified by oxidative events and by the action of lipolytic and proteolytic enzymes with the generation of products that exhibit atherothrombogenic potential. The role of the O-glycans linked to the inter-kringle linkers of apolipoprotein(a) is also emerging. This information is raising the awareness of the pleiotropic functions of Lp(a) and is opening new vistas on pathogenetic mechanisms whose knowledge is essential for developing rational therapies against this complex cardiovascular pathogen.

Lysine-Phosphatidylcholine Adducts in Kringle V Impart Unique Immunological and Potential Pro-inflammatory Properties to Human Apolipoprotein(a)

“…From the cardiovascular standpoint, various mechanisms have been suggested to explain the athero-thrombogenic potential of Lp(a) and distinct domains in apo(a) have been identified for each reported function (1). Recently, we have shown that apo(a), its C-terminal domain and one of the fragments comprising the KV-PD region stimulated the production and secretion of IL-8 in human THP-1 macrophages grown in culture (5).…”

“…The other kringles, classified from 1 to 10, occur as a single copy each differing in amino acid sequence (1). The function of some of these kringles has been recognized.…”

“…The function of some of these kringles has been recognized. For instance, the microdomain comprising KIV-5 through KV-8 has been reported to be involved in the first step of non-covalent interaction between apo(a) and apoB100, and KIV-9 via its unpaired cysteine is responsible for the formation of the disulfide bond that stabilizes the interaction between apo(a) and apoB100 (1,2). Moreover, KIV-10 contains the high affinity lysine binding site that plays a dominant role in the binding of apo(a) to fibrin(ogen) and components of the vascular extracellular matrix (3).…”

Association of Elevated Serum Lipoprotein(a), Inflammation, Oxidative Stress and Chronic Kidney Disease with Hypertension in Non-diabetes Hypertensive Patients

“…Lipoprotein(a) is an atherogenic particle, that is a LDLlike substance which structure is apolipoprotein(a) [Apo(a)] attached with disulfide bond to apolipoprotein B-100 on the LDL core [4]. Apo(a) is synthesized and secreted into the circulation by liver.…”

Comparative Study of Lipoprotein (A) Level in Type 2 Diabetics and Non Diabetics with Acute Coronary Syndrome

“…Lipoprotein (a) (Lp (a)) has been established as an independent risk factor for CAD. (2) . Therefore, this study was designed to compare the serum Lp (a) level in patients with type 2 diabetes and nondiabetic individuals.…”