Harald Torsvik

Familial Plasma Cholesterol Ester Deficiency a study of the erythrocytes

The erythrocytes of three sisters with plasma cholesterol ester deficiency and lack of plasma lecithin: cholesterol acyltransferase (LCAT) have been studied. The erythrocyte content of cholesterol was markedly increased. Their total lipid phosphorus was normal, lecithin being increased and phosphatidylethanolamine and sphingomyelin decreased. The fatty acid composition of the phospholipids was not normal as an increase in linoleic acid and a decrease in arachidonic and very long chain fatty acids were demonstrated. The absence of LCAT in plasma of the patients may explain the major lipid abnormalities of their red cells.

Identification of the abnormal cholestatic lipoprotein (LP-X) in familial lecithin:Cholesterol acyltransferase deficiency.

Virtually all lipids of human plasma circulate in association with specific proteins to yield lipid-protein complexes or lipoproteins. The lipoproteins are conventionally classified into four main groups based on ultracentrifugal flotation or electrophoretic mobility: chylomicrons, very low density lipoprotein (VLDL) or pre+lipoprotein, low density lipoprotein (LDL) or @lipoprotein, and high density lipoprotein (HDL) or ol -lipoprotein. According to the chemical classification system [l] , plasma lipoproteins consist of a mixture of polydisperse lipoprotein families each of which is characterized by the presence of a single, distinct apolipoprotein or its constitutive poly peptides: lipoprotein family LP-A is characterized by apolipoprotein A, lipoprotein family LP-B by apelipoprotein B and lipoprotein family LP-C by ape lipoprotein C. In sera of normal subjects and most patients with hyperlipoproteinemia of different types, 60-80% of the cholesterol is esterified. However, the levels of esterified cholesterol have been reported to be very low in obstructive jaundice [2 ] and in familial lecithin:cholesterol acyltransferase (LCAT) deficiency [31-

Serum lipoproteins in plasma lecithin:cholesterol acyltransferase deficiency, studied by electron microscopy

Serum lipoproteins from a patient with LCAT deficiency have been studied by electron microscopy and compared with lipoproteins from a normal individual and a patient with hyperlipo‐proteinemia of type IV. Particles of density < 1.006 g/ml from the LCAT deficiency patient were within a range of 230–3000 Å in diameter, whereas the diameters of the corresponding particles from the other two subjects fell within a range from 230 to 900 Å. A mean diameter of approximately 200 Å was found for the low density lipoproteins (l.019–1.063 g/ml) from the three subjects investigated.

Changes in Lp(a) lipoprotein and other plasma proteins during acute myocardial infarction

The sequential changes of Lp(a) lipoprotein concentrations in patients (n=59) suffering acute myocardial infarction (AMI) were examined and compared with other plasma proteins. The temporal and quantitative characteristics of the responses in concentration of acute phase reactants (CRP, haptoglobin, α1‐antitrypsin, α‐acid glycoprotein), lipids (total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol) and apolipoproteins AI and B were similar to previous reports. Lp(a) lipoprotein showed transient changes with an initial decrease of 10–25% compared to the 3‐month control value, followed by rebound on day 7–11 above admission level, before again declining. We were able to demonstrate a quantitative relationship between infarct size and alterations in plasma levels of acute phase reactants. However, in addition to rather unusual significant fluctuations during AMI, Lp(a) lipoprotein changes seemed unrelated to infarct size. These findings do not support the view that Lp(a) lipoprotein acts as an acute phase reactant.

Presence of α1-Lipoprotein in Patients with Familial Plasma Lecithin:Cholesterol Acyltransferase Deficiency

Three sisters with plasma lecithin: cholesterol acyltransferase deficiency have been studied. Precipitates were demonstrated between their serum and anti-α1-lipoprotein by Ouchterlony technique. The α1-lipoprotein of the patients exhibited atypical behaviour in immunoelectrophoretic tests, in preparative ultracentrifugation, and by gel filtration on Sephadex G-200.

Studies on the protein moiety of serum high density lipoprotein from patients with familial lecithin: cholesterol acyltransferase deficiency

Serum high density lipoproteins (HDL) from three patients with lecithin: cholesterol acyltransferase (LCAT) deficiency have been studied. HDL from the patients is composed of two components, one of high molecular weight (HM‐HDL) and one of relatively low molecular weight (LM‐HDL). The polypeptides of lipid‐free HDL (apoHDL) from normal subjects were indistinguishable from those of apoHM‐HDL from the patients as judged by treatment with 8 M urea and gel filtration on Sephadex G‐200, immunological experiments, disc electrophoresis, and amino acid analysis. ApoLM‐HDL contained mainly the apoA‐I polypeptide with small amounts of apoA‐II, whereas C‐polypeptides were lacking. The results indicate that the presence of apparently “abnormal” HDL particles in serum of the patients is secondary to the lack of LCAT activity.

Apolipoproteins and lipoprotein families in familial lecithin: cholesterol acyltransferase deficiency.

The plasma lipoprotein system in patients with familial LCAT deficiency contains all the polypeptides and lipoprotein families identified previously in plasma lipoproteins of normal subjects. There are, however, some qualitative and quantitative differences. The most significant qualitative difference is the presence in LCAT-deficient plasma of LP-X, the abnormal low density lipoprotein species characteristic of obstructive jaundice. The major quantitative difference is the reduced concentration of ApoA, ApoB, and ApoD in LCAT-deficient plasma. It has already been demonstrated that most lipoprotein species in LCAT deficiency have an abnormal lipid composition characterized by unusually high contents of unesterified cholesterol and lecithin and a negligible amount of esterified cholesterol (4). These abnormalities of the lipoprotein system in familial LCAT deficiency seem to result from the virtual absence of LCAT activity rather than from the absence of normally occurring lipoprotein families or their con...

Further studies on serum α1-lipoprotein in familial lecithin:cholesterol acyltransferase deficiency

Serum high density lipoprotein (HDL) from two patients with LCAT deficiency has been compared with HDL from normal subjects and HDL from a presumed heterozygous carrier. By two different immunological methods the concentration of ‐lipoprotein in serum of the patients was found to he about 25–30 % of the normal concentration.

Preliminary assignment of the inherited Hl 1 antigen to the apoA-I polypeptide of rabbit high density lipoprotein

The first genetic polymorphism of serum high density lipoprotein (HDL) in any species was found by Berg et al. [I] in the rabbit. The presence or absence of an antigen designated Hl 1 appeared to be controlled by autosomal dominant inheritance. In human serum the protein moiety of HDL is known to contain at least five polypeptide chains [2,3]. The two main polypeptides are called ApoA-I and ApoA-II according to the nomenclature of Kostner and Alaupovic [4]. The other three polypeptides ApoC-I, ApoC-II, and ApoC-III, constituting about 10% of the HDL apoprotein are also the major components of the protein moiety of very low density lipoprotein (VLDL) [.5]. In this report we present data which indicate that also rabbit HDL is composed of several polypeptides with a pattern resembling that of man, and that the Hl 1 antigen resides in one of the two major polypeptides.

Studies on the pre-α-lipoprotein of human serum II. Evidence for the presence of an albumin-Apo-A-I complex

By combined column affinity chromatography and preparative electrophoresis, a lipoprotein was isolated from the electrophoretically defined pre-alpha-region. The isolated fraction, designated Fraction II1, demonstrated one band after electrophoresis in agarose, in polyacrylamide, and in sodium dodecylsulphate containing polyacrylamid. Double diffusion experiments disclosed the presence of albumin and apolipoprotein-A-I within the fraction. After reduction with mercaptoethanol and subsequent electrophoresis in sodium dodecylsulphate containing polyacrylamide gel, two bands appeared. One of the bands had an electrophoretic mobility similar to albumin monomer (mol.wt 67,000), the other had the same electrophoretic mobility as apolipoprotein-A-I with a mol.wt of 28,400. It is suggested that Fraction II1 contains an albumin-apolipoprotein-A-I complex.