Sialic acid metabolism as a potential therapeutic target of atherosclerosis

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.

Keywords: Atherosclerosis; Sialic acid; Sialidase; Sialyltransferase; Trans-sialidase.

Fig. 1

The summary of mammalian Sia metabolism and the Neu5Ac-activated signaling pathway in cardiomyocyte. Legend: In eukaryotic cells, Neu5Ac is synthesized in cytoplasm and transferred to nucleus for cytosine 5′-monophosphate (CMP)-Neu5Ac synthesis by CMP-Neu5Ac activating acid. Then, it is transmitted to Golgi apparatus to form glycoconjugates by ST, which is subsequently secreted or delivered to cell surface. N-Acetyl-Neuraminic Acid (Neu5Ac) as a signaling molecule to trigger myocardial injury via activation of Rho/ROCK-JNK/ERK signaling pathway in acute myocardial infarction