Hematological Inflammatory Markers in Patients with Clinically Confirmed Familial Hypercholesterolemia.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder of lipid metabolism which leads to premature cardiovascular diseases. In patients with FH, blood inflammatory markers may be disrupted; however, its extent is unclear. In this study, we aimed to evaluate the NLR (neutrophil to lymphocyte ratio), PLR (platelet count to lymphocyte count ratio), MPV (mean platelet volume), RPR (red blood cell distribution width to platelet count ratio), WBC (white blood cell), and PDW (platelet distribution width and platelet count). METHODS: The patients were selected from laboratories due to high cholesterol level and who had history of premature cardiovascular disease. The Dutch Lipid Clinic Network (DLCN) criteria are used for the detection of FH. Controls had a history of hyperlipidemia, and both groups could be on pharmacotherapy or not. All the biochemical markers were evaluated using appreciate methods. Statistical analysis was done using STATA 14. RESULTS: The study group consisted of 1074 patients with FH and 473 control cases. Of the CBC inflammatory markers, only PLR was significantly (p value = 0.003) higher in FH patients (7.96 ± 10.08) compared to non-FH (6.45 ± 2.44). In FH patients, the PLR was significantly higher in probable/definite FH group (9.70 ± 14.06) compared to possible FH (7.36 ± 8.23) (p value < 0.001). Linear regression analysis showed that only RLR was independently associated with total cholesterol (b = 0.000, p = 0.13). CONCLUSIONS: Our results may show the importance of high cholesterol on platelet activity and highlight the use of lipid lowering drugs in patients with hyperlipidemia.

Expression of biologically active human clotting factor IX in Drosophila S2 cells: γ-carboxylation of a human vitamin K-dependent protein by the insect enzyme.

The Drosophila γ-glutamyl carboxylase (dγC) has substrate recognition properties similar to that of the vertebrate γ-carboxylase (γC), and its carboxylated product yield, in vitro, was shown to be more than that obtained with the human enzyme. However, whether the Drosophila enzyme is able to γ-carboxylate the human vitamin K-dependent (VKD) proteins, such as the human coagulation factor IX (hFIX), as synthesized in cultured Drosophila cells was not known. To examine this possibility, the Drosophila Schnider (S2) cell line was transfected with a metallothionein promoter-regulated hFIX-expressing plasmid. After induction with copper ion, expression efficiency of the active hFIX was analyzed by performing enzyme-linked immunosorbent assey (ELISA) and coagulation test on the culture supernatant of the transfected S2 cells during 72 h of postinduction. In comparison with Chinese hamster ovary cell line, S2 cells showed higher (≈ 12-fold) expression level of the hFIX. The γ-carboxylation of the Drosophila-derived hFIX was confirmed by evaluation of the expressed protein, after being precipitated with barium citrate. The biological activity of the S2 cell-derived hFIX indicated the capability of S2 cells to fulfill the required γ-carboxylation of the expressed hFIX. Coexpression of the human γ-glutamyl carboxylases (hγC) was also shown to improve both expression and γ-carboxylation of the hFIX. This is the first in vivo data to describe the ability of the dγC to recognize the human-based propeptide as substrate, which is an essential step for production of biologically active γ-carboxylated VKD proteins.