【論文摘要】Sialidase Activity Responsible for Atherogenic Modification of LDL Varies Seasonally in the Blood of Atherosclerotic Patients; Influenza Sialidase Involvement

Alexander Orekhov ； Dmitry Kashirskikh ； Victoria Khotina ； Igor Sobenin

《海峽循環醫學雜誌》 1卷2S期 (2019/09) Pp. 65-65

https://doi.org/10.6907/SCJ.201909/SP_1(2).0055

摘要

Background/Synopsis: We have found multiple-modified low-density lipoprotein (LDL) in the blood of atherosclerotic patients. Modified LDL is able to induce accumulation of lipids in human monocytes and in smooth muscle cells cultured from unaffected intima of human aorta. Along with small size, high density and increased electronegative charge, modified LDL is characterized by decreased level of sialic acid. Negative correlation between the level of sialic acid in LDL and its ability to induce accumulation of intracellular cholesterol has been found. Thus, desialylation is an atherogenic modification of LDL. In the blood of atherosclerotic patients, we have discovered a soluble enzyme belonging by its donor-acceptor properties to trans-sialidases. Objectives/Purpose: It is known that the risk of atherosclerotic diseases, in particular coronary heart disease, increases in winter. In the present study, we evaluated the sialidase activity in the blood of atherosclerotic patients in the autumn-winter and spring-summer season. Methods/Results: Lipoprotein-deficient serum obtained by ultracentrifugation was used for isolation of trans-sialidase by the affinity chromatography with a-2,8-Neu5Ac- sepharose. After washing, sorbent-bound protein fraction was eluted with 50 mM sialic acid. Sialidase activity was measured in blood samples from 326 CHD patients (172 men, 154 women), mean age 63.6 (SD=12.2) by radiologic assay and commercially available fluorometric assay (Abcam ab138888 Neuraminidase Assay Kit). To detect expression of infuenza virus neuraminidase, qPCR with degenerate primers was performed. We have revealed seasonal differences in trans-sialidases activity in blood serum of 61% observed patients. More than 43% of patients had higher level of trans-sialidase activity in winter as compared with summer period. The opposite situation occurred in 17% of patients. Thereby, we could conclude that the most part of observed subjects have higher blood serum sialidase activity in winter period. This correlates well with seasonal dynamics of heart disease risk. It is known that viruses have high sialidase activity. We have assumed that seasonal differences can be determined by viral infection. To check this hypothesis we have evaluated the expression of the influenza virus sialidase genes in the blood of patients. Using PCR, we have detected expression of viral sialidase in the blood of atherosclerotic patients. Conclusion: Thus, trans-sialidase activity and the level of modified LDL in human blood serum can serve as the additional factors for estimation of cardiovascular disease risk; sialidase activity in the blood of atherosclerotic patients is at least partially determined by viral sialidase.