Sialidases: Therapeutic and Antiatherogenic Potential

Abstract

This review focuses on the biological role and clinical relevance of relatively poor studied enzymes known as sialidases. We describe structure and function of sialic acid, in particular as a component of gangliosides and plasma lipoproteins. Several types of sialidases are known in mammals, of which trans-sialidase is of special interest, since it is capable of removing sialic acid from low density lipoprotein (LDL) particles and transferring it to different acceptors in blood plasma. Desialylation of LDL, in turn, endows it a capacity to accumulate in the smooth muscle cells of human aortic intima, and therefore is important for atherogenesis. Moreover, sialidases appear to be involved in a variety of pathological processes, including viral infections and cancer, which makes these enzymes an attractive therapeutic target.

The Atherogenic Role of Circulating Modified Lipids in Atherosclerosis

“…The studies indicated that there is a difference between the activity and specificity of sialidases in atherosclerotic lesions and unaffected intima [81]. Additionally, it was found that the diminished trans-sialidase activity in the blood directly correlates with the lower ability of blood serum to induce cholesterol accumulation in a culture of unaffected human aortic intimal cells [82]. Indeed, the activity of trans-sialidase in human plasma determines blood atherogenic properties.…”

“…Furthermore, trans-sialidase can change the lipoprotein interaction with the arterial cells. It was shown that LDL desialylated by trans-sialidase causes intracellular accumulation of lipids, in association with stimulation of the proliferative activity of vascular cells and synthesis of extracellular matrix components [82]. Moreover, sialidases can change the activity of many blood cells and lipoproteins.…”

“…To date, none of the direct anti-atherosclerotic therapeutic methods is known. Therefore, a novel therapeutic approach, such as the use of trans-sialidase inhibitors was suggested [82]. Using trans-sialidase inhibitors may prevent LDL from desialylation and consequently from the formation of foam cells.…”

“…Using trans-sialidase inhibitors may prevent LDL from desialylation and consequently from the formation of foam cells. It was demonstrated in apoE −/− mice that administration of a sialidase inhibitor 2-deoxy-2,3-dihydro- N -acetylneuraminic acid (DANA) had an anti-atherogenic effect [82]. The activity of trans-sialidase in human blood plasma was also decreased with the use of some plant-derived extracts.…”

Comparison of the Protective Effects of Individual Components of Particulatedtrans-Sialidase (PTCTS), PTC and TS, against High Cholesterol Diet-Induced Atherosclerosis in Rabbits

“…Compared to native LDL, desialylated LDL has a higher capacity to bind to asialoglycoprotein receptor, a high capacity C-type lectin receptor, mainly expressed on hepatocytes. The interaction of desialylated LDL particles with this scavenger receptor leads to their uptake by the cell and hence to their intracellular accumulation due to reduced degradation [ 25 ]. The removal of sialic acid from LDL by neuraminidase was also found to enhance the atherogenic potential of LDL particles by increasing their capacity to accumulate intracellular cholesterol content in smooth muscle cells and macrophages [ 26 ].…”