The Mysteries Of Lipoprotein(a)

Lipoprotein(a) [Lp(a)] is a macromolecular complex found in human plasma that combines structural elements from the lipoprotein and blood clotting systems and that is associated with premature coronary heart disease and stroke. It is assembled from low-density lipoprotein (LDL) and a large hydrophilic glycoprotein called apolipoprotein(a) [apo(a)], which is homologous to the protease zymogen plasminogen. Plasma Lp(a) concentrations vary 1000-fold between individuals and represent a continuous quantitative genetic trait with a skewed distribution in Caucasian populations. Variation in the hypervariable apo(a) gene on chromosome 6q2.6-q2.7 and interaction of apo(a) alleles with defective LDL-receptor genes explain a large fraction of the variability of plasma Lp(a) concentrations. Though of high theoretical and practical interest, many aspects of the metabolism, function, evolution, and regulation of plasma concentrations of Lp(a) are presently unknown, controversial, or mysterious. [1]

Lipoprotein Metabolism

Plasma lipoprotein levels are related to a process in humans—arteriosclerosis and, in particular, to its clinical manifestation, coronary artery disease. The biochemistry, biophysics, and physiology of plasma lipoproteins have been reviewed. Lipoproteins are the transport vehicle in plasma for the water-insoluble lipids from their organs of synthesis to their sites of utilization. Lipoproteins are found in plasma as discrete entities, containing lipids and specific proteins. To understand the biological processes involved in the metabolism of lipoproteins and the regulatory mechanisms affecting their plasma levels, they must be regarded as complex particles of unique composition, structure, and function. This chapter discusses lipoprotein metabolism using an approach that integrates the composition, structure, and function of lipoproteins and regards lipoproteins as discrete and finite particles. It presents the data concerning lipoprotein structure and composition. The chapter discusses the synthesis and catabolism of lipoproteins as they relate to the whole lipoprotein particle. These routes are correlated with the mechanisms operating in the regulation of plasma lipoprotein levels and their possible relationship to lipid transport disorders. [2]

Lipoprotein(a): intrigues and insights

Lipoprotein(a) is an atherogenic, cholesterol ester-rich lipoprotein of unknown physiological function. The unusual species distribution of lipoprotein(a) and the extreme polymorphic nature of its distinguishing apolipoprotein component, apolipoprotein(a), have provided unique challenges for the investigation of its biochemistry, genetics, metabolism and atherogenicity. Some fundamental questions regarding this enigmatic lipoprotein have escaped elucidation, as will be highlighted in this review.[3]

Lipoprotein (a) Particles Characterization by Dynamic Light Scattering

Lp(a) is a novel cardiovascular risk factor resembling an LDL particle. It includes a copy of apolipoprotein (a) [apo(a)], whose molecular weight is dependent on the number of genetically encoded kringle IV type 2 (KIV-2) repeats and inversely related with Lp(a) plasma concentration and risk. The reason for this inverse relationship is unclear and, particularly, there are no data regarding the size of Lp(a) particles carrying apo(a) with different molecular weights. The aim of the present work was to explore if a relationship existed between apo(a) molecular weight and particles size in Lp(a) samples carrying 20, 25 and 28 KIV-2 repeats (K20, K25 and K28, respectively). Dynamic Light Scattering (DLS) measurements were performed on affinity-purified Lp(a). A preliminary finding was that particles were typically distributed into three different size groups instead of the single one expected. No difference in average particle size between Lp(a) carrying different apo(a) isoforms was found. However, the percentage of medium-sized particles in each sample was found to be inversely related to the number of KIV-2 repeats (R2=0.99), with a clear predominance in K20 (58.53%). These data deserve further investigations, as they might be potentially relevant to explain the pathogenic role of low molecular weight Lp(a) isoforms. [4]

Plasma Lipoprotein Profile in Newly Hatched Chicks Following in Ovo Ghrelin Administration

Objective: The aim of this study was to investigation on effects of in ovo administrated exogenous ghrelin on plasma lipid profile in hatched broiler chicks.

Methodology: 250 eggs were obtained from commercial broiler breeder (Ross 308 strain) farm. the eggs were divided into five experimental groups; T1 or eggs without any injection (control), T2 or eggs in ovo injected with 50ng ghrelin at embryonic day-5, T3 or eggs in ovo injected with 100ng ghrelin at embryonic day-5, T4 or eggs in ovo injected with 50ng ghrelin at embryonic day-10, and T5 or eggs in ovo injected with 100ng ghrelin at embryonic day-10. Similar in ovo experiments were done for all of injected groups on day-5 or -10. At end of incubation, blood samples from each group were collected following chick decapitation and analyzed for determination of plasma lipoprotein concentrations.

Results: Exogenous ghrelin administration at different embryonic days couldn’t have any considerable effect on low density lipoprotein (LDL-C), very low density lipoprotein (VLDL-C) or high density lipoprotein (HDL)/LDL-C. Plasma HDL-C concentration had increase follow in ovo injection of 100ng ghrelin at day-5 (P<0.01) and had slight increase at day-10 (group T3 and T5).

Conclusion: As conclusion, in ovo administration of 100ng ghrelin at embryonic day-5 could elevate plasma HDL-C concentrations of newly-hatched chicks without any significant effect on LDL-C, VLDL or HDL-LDL ratio. [5]

Reference

[1] Utermann, G., 1989. The mysteries of lipoprotein (a). Science, 246(4932), pp.904-910.

[2] Eisenberg, S. and Levy, R.I., 1975. Lipoprotein metabolism. Advances in lipid research, 13, pp.1-89.

[3] Hobbs, H.H. and White, A.L., 1999. Lipoprotein (a): intrigues and insights. Current opinion in lipidology, 10(3), pp.225-236.

[4] Pasquetto, V., Santonastaso, A., Grandi, S., Derosa, G., D’Angelo, A. and Scotti, C., 2016. Lipoprotein (a) Particles Characterization by Dynamic Light Scattering. Journal of Advances in Medicine and Medical Research, pp.1-8.

[5] Lotfi, A., Shahryar, H.A. and Narimani-Rad, M., 2011. Plasma lipoprotein profile in newly hatched chicks following in ovo ghrelin administration. Annual Research & Review in Biology, pp.117-122.