Page 116 - Read Online
P. 116

Alipov et al.                                                                                                                                                        Difference between native and desialylated LDL

           apoA-IV,  and  apoF],  associated  with  inflammation
           (apoD, apoJ, apoM, serum amyloid A4, paraoxonase 1,
           prenylcysteine  oxidase  1,  migration  inhibitory  factor-
           related protein 8, and retinol binding protein), related with
           thrombosis (fibrinogen alpha chain) and components
           of the innate immunity system (lysozyme C, alpha-1
           antitripsin, apoL-1, and transthyretin). [10]  ApoB-100 is a
           large glycoprotein, which stabilizes and maintains LDL
           structure and composition. ApoB-100 has 24 potential
           N-glycosylation sites, with up to 16 asparagine residues
           actually glycosylated. Carbohydrates, including neutral
           and acidic carbohydrate chains, account for 5-9%
           of apoB-100 molecular weight.  All chains contain
           N-acetylglucosamine and mannose residues. Acidic
           chains  contain  terminal sialic  acid residues  followed
           by galactose [Figure 1]. [36-38]  Loss of the terminal sialic
           acid residue results in exposure of galactose residues.   Figure 1: Carbohydrate chains in apoB-100. Both chains
           It was suggested that almost all nLDL particles    have  mannose  base  (Man)  connected  to  polypeptide  chain  by
                                                              N-acetylglucosamine (GlcNAc). Acidic one has terminal sialic acid
           are  partially  monodesialylated  because  they  have   residues connected to galactose (Gal) molecules. [36-38]
           galactose ending chains. [39]

                                                              the  same,  except  for  sialic  acid  level,  which  was
           The phospholipid monolayer contains phosphatidylcholine,   significantly (1.6 times) lower in patient LDL (P < 0.05)
           sphingomyelin,  lysophosphatidylcholine,  phosphatidyl-  [Figure 2]. [40]   There  was  no  significant  difference  in
           ethanolamine,  ceramide, and diacylglycerol. The
           hydrophobic core contains various lipid classes: non-  the levels of galactose, N-acetyl glucosamine and
           esterified cholesterol, cholesterol esters, and triglycerides.   mannose between nLDL and modified LDL from healthy
           Non-esterified  cholesterol  is  also  located  on  the   donors, as well as from patients with atherosclerosis.
           surface of the LDL particle. nLDL transports 66% of   Sialic  acid  content  in  modified  LDL  was  30%  lower
           serum  gangliosides.  Gangliosides  are  sialic-acid-  than in nLDL from healthy subjects. Sialic acid level in
           rich glycosphingolipids and are thought  to contain   modified LDL from patients was 2 to 3 fold lower than
           all  the sialic  acid residues associated with the LDL   in nLDL. Comparison of nLDL obtained from healthy
           lipids. [36]   The  lipid  part  of  nLDL  also  contains  other   subjects and patients with atherosclerosis revealed
           monosaccharides: galactosamine and glucose. [40]   no  significant  differences  in  carbohydrate  contents.
                                                              Modified LDL had a significantly lower level of sialic
           First studies of LDL carbohydrate composition revealed   acid (P < 0.05). There was also a significant difference
           little or no variation in glucosamine, galactose and   in the sialic acid content between modified LDL from
           mannose values, but a marked variation in sialic acid   healthy donors and from patients with atherosclerosis,
           levels  [Table 1].  Further studies showed that in   P < 0.05.
                          [41]
           patients with coronary artery disease (CAD), LDL had
           a  decreased  sialic  acid  content.  Isolated  LDL  from   Levels of all lipid-associated carbohydrates were 1.5 to 2
           these patients, as well as  in vitro desialylated LDL,   fold lower in LDL samples obtained from atherosclerosis
           caused atherogenic changes in cultured cells. [13,42,43]  The   patients in comparison to those from healthy subjects.
           most  comprehensive  study  on  chemical  composition   Native  and  modified  LDL  obtained  from  patients  and
           of LDL in patients with and without atherosclerosis   healthy subjects also differed by lipid composition.
           was  performed  in 1993. [40]   Carbohydrate content  of   Modified  LDL  had  decreased  levels  of  cholesterol,
           LDL from patients with atherosclerosis was almost   cholesterol esters, triglycerides, phosphatidylcholine,

           Table 1: Carbohydrate content of LDL according to early studies (percent dry weight)
                                              Sialic acid     Glucosamine       Galactose         Mannose
           Schultze and Heide [87]  (1960)       1.5              2.0              2.7              2.7
           Ayrault-Jarrier [88]  (1961)          1.3              1.2               -                -
           Marshall and Kummerow [89]  (1962)    0.35             1.2                  3.23 (together)
           Kwiterovich et al. [90]  (1974)       0.6              0.9              1.8              3.7
                               [41]
           Swaminathan and Aladjem  (1976)       1.73             0.94             2.13             4.88
           LDL: low density lipoprotein; “-”: not measured
                           Vessel Plus ¦ Volume 1 ¦ September 26, 2017                                    109
   111   112   113   114   115   116   117   118   119   120   121