Sialic Acid Metabolism As a Potential Therapeutic Target of Atherosclerosis

Overview

Journal Lipids Health Dis

Publisher Biomed Central

Specialties Biochemistry
Endocrinology

Date 2019 Sep 16

PMID 31521172

Citations 34

Authors

Chao Zhang

Jingyuan Chen

Yuhao Liu

Danyan Xu

Affiliations

Soon will be listed here.

Abstract

Sialic acid (Sia), the acylated derivative of the nine-carbon sugar neuraminic acid, is a terminal component of the oligosaccharide chains of many glycoproteins and glycolipids. In light of its important biological and pathological functions, the relationship between Sia and coronary artery disease (CAD) has been drawing great attentions recently. Large-scale epidemiological surveys have uncovered a positive correlation between plasma total Sia and CAD risk. Further research demonstrated that N-Acetyl-Neuraminic Acid, acting as a signaling molecule, triggered myocardial injury via activation of Rho/ROCK-JNK/ERK signaling pathway both in vitro and in vivo. Moreover, there were some evidences showing that the aberrant sialylation of low-density lipoprotein, low-density lipoprotein receptor and blood cells was involved in the pathological process of atherosclerosis. Significantly, the Sia regulates immune response by binding to sialic acid-binding immunoglobulin-like lectin (Siglecs). The Sia-Siglecs axis is involved in the immune inflammation of atherosclerosis. The generation of Sia and sialylation of glycoconjugate both depend on many enzymes, such as sialidase, sialyltransferase and trans-sialidase. Abnormal activation or level of these enzymes associated with atherosclerosis, and inhibitors of them might be new CAD treatments. In this review, we focus on summarizing current understanding of Sia metabolism and of its relevance to atherosclerosis.

Citing Articles

Atherosclerosis: A Comprehensive Review of Molecular Factors and Mechanisms.

Tasouli-Drakou V, Ogurek I, Shaikh T, Ringor M, DiCaro M, Lei K Int J Mol Sci. 2025; 26(3).

PMID: 39941130 PMC: 11818631. DOI: 10.3390/ijms26031364.

Comprehensive Analysis of Sialylation-Related Gene Profiles and Their Impact on the Immune Microenvironment in Periodontitis.

Wu Q, Niu Y, Li H, Pan Y, Li C Inflammation. 2024; .

PMID: 39609348 DOI: 10.1007/s10753-024-02177-1.

N-Acetylneuraminic acid triggers endothelial pyroptosis and promotes atherosclerosis progression via GLS2-mediated glutaminolysis pathway.

Liu Z, Xiang P, Zeng S, Weng P, Wen Y, Zhang W Cell Death Discov. 2024; 10(1):467.

PMID: 39537619 PMC: 11561128. DOI: 10.1038/s41420-024-02233-7.

Effect of green coffee on miR-133a, miR-155 and inflammatory biomarkers in obese individuals.

Khedr N, Zahran E, Ebeid A, Melek S, Werida R Diabetol Metab Syndr. 2024; 16(1):256.

PMID: 39468643 PMC: 11520395. DOI: 10.1186/s13098-024-01478-7.

Supplementing Glucose Intake Reverses the Inflammation Induced by a High-Fat Diet by Increasing the Expression of Siglec-E Ligands on Erythrocytes.

Liu H, Li J, Wu N, She Y, Luo Y, Huang Y Inflammation. 2024; 47(2):609-625.

PMID: 38448631 DOI: 10.1007/s10753-023-01932-0.

References

Millar J, Anber V, Shepherd J, Packard C . Sialic acid-containing components of lipoproteins influence lipoprotein-proteoglycan interactions. Atherosclerosis. 1999; 145(2):253-60. DOI: 10.1016/s0021-9150(99)00071-4. View

Wu E, Lumb P, Chambers J, Crook M . Plasma sialic acid and coronary artery atheromatous load in patients with stable chest pain. Atherosclerosis. 1999; 145(2):261-6. DOI: 10.1016/s0021-9150(99)00074-x. View

Lindbohm N, Gylling H, Miettinen T, Miettinen T . Statin treatment increases the sialic acid content of LDL in hypercholesterolemic patients. Atherosclerosis. 2000; 151(2):545-50. DOI: 10.1016/s0021-9150(99)00425-6. View

Hartnell A, Steel J, Turley H, Jones M, Jackson D, Crocker P . Characterization of human sialoadhesin, a sialic acid binding receptor expressed by resident and inflammatory macrophage populations. Blood. 2001; 97(1):288-96. DOI: 10.1182/blood.v97.1.288. View

Tertov V, Kaplun V, Sobenin I, Boytsova E, Bovin N, Orekhov A . Human plasma trans-sialidase causes atherogenic modification of low density lipoprotein. Atherosclerosis. 2001; 159(1):103-15. DOI: 10.1016/s0021-9150(01)00498-1. View

Yogeeswaran G, Hakomori S . Cell contact-dependent ganglioside changes in mouse 3T3 gibroblasts and a suppressed sialidase activity on cell contact. Biochemistry. 1975; 14(10):2151-6. DOI: 10.1021/bi00681a017. View

Gracheva E, Samovilova N, Golovanova N, Ilinskaya O, Tararak E, Malyshev P . Sialyltransferase activity of human plasma and aortic intima is enhanced in atherosclerosis. Biochim Biophys Acta. 2002; 1586(1):123-8. DOI: 10.1016/s0925-4439(01)00093-x. View

cerne D, Jurgens G, Ledinski G, Kager G, Greilberger J, Lukac-Bajalo J . Relationship between the sialic acid content of low-density lipoprotein (LDL) and autoantibodies to oxidized LDL in the plasma of healthy subjects and patients with atherosclerosis. Clin Chem Lab Med. 2002; 40(1):15-20. DOI: 10.1515/CCLM.2002.004. View

Suer Gokmen S, Kilicli G, Ozcelik F, Ture M, Gulen S . Association between serum total and lipid-bound sialic acid concentration and the severity of coronary atherosclerosis. J Lab Clin Med. 2002; 140(2):110-8. DOI: 10.1067/mlc.2002.126344. View

10.

Gavella M, Lipovac V, Car A, Vucic M, Sokolic L, Rakos R . Serum sialic acid in subjects with impaired glucose tolerance and in newly diagnosed type 2 diabetic patients. Acta Diabetol. 2003; 40(2):95-100. DOI: 10.1007/s005920300012. View

11.

Matsukawa N, Nariyama Y, Hashimoto R, Kojo S . Higher reactivity of apolipoprotein B-100 and alpha-tocopherol compared to sialic acid moiety of low-density lipoprotein (LDL) in radical reaction. Bioorg Med Chem. 2003; 11(18):4009-13. DOI: 10.1016/s0968-0896(03)00392-4. View

12.

Tertov V, Sobenin I, Orekhov A . Characterization of desialylated low-density lipoproteins which cause intracellular lipid accumulation. Int J Tissue React. 1992; 14(4):155-62. View

13.

Vaya A, Falco C, Reganon E, Vila V, Martinez-Sales V, Corella D . Influence of plasma and erythrocyte factors on red blood cell aggregation in survivors of acute myocardial infarction. Thromb Haemost. 2004; 91(2):354-9. DOI: 10.1160/TH03-08-0497. View

14.

Orekhov A, Tertov V, Sobenin I, Smirnov V, Via D, Guevara Jr J . Sialic acid content of human low density lipoproteins affects their interaction with cell receptors and intracellular lipid accumulation. J Lipid Res. 1992; 33(6):805-17. View

15.

Varki A . Diversity in the sialic acids. Glycobiology. 1992; 2(1):25-40. PMC: 7108601. DOI: 10.1093/glycob/2.1.25. View

16.

Cuniberti L, Martinez V, Schachter J, Magarinos G, Cabeza Meckert P, Laguens R . Sialic acid as a protective barrier against neointima development. Atherosclerosis. 2005; 181(2):225-31. DOI: 10.1016/j.atherosclerosis.2005.01.021. View

17.

Ogden C, Kowalewski R, Peng Y, Montenegro V, Elkon K . IGM is required for efficient complement mediated phagocytosis of apoptotic cells in vivo. Autoimmunity. 2005; 38(4):259-64. DOI: 10.1080/08916930500124452. View

18.

Inayat-ur-Rahman , Malik S, Khan W . Relation of serum sialic acid with serum lipids in cardiac patients. Pak J Pharm Sci. 2005; 18(3):71-3. View

19.

Boisvert W, Rose D, Johnson K, Fuentes M, Lira S, Curtiss L . Up-regulated expression of the CXCR2 ligand KC/GRO-alpha in atherosclerotic lesions plays a central role in macrophage accumulation and lesion progression. Am J Pathol. 2006; 168(4):1385-95. PMC: 1606562. DOI: 10.2353/ajpath.2006.040748. View

20.

Gopaul K, Crook M . Sialic acid: a novel marker of cardiovascular disease?. Clin Biochem. 2006; 39(7):667-81. DOI: 10.1016/j.clinbiochem.2006.02.010. View