Modified citrus pectin inhibits galectin-3 function to reduce atherosclerotic lesions in apoE-deficient mice.

Abstract

Galectin-3 is a carbohydrate-binding lectin, which has been implicated in the modulation of atherosclerotic pathophysiology, and is highly expressed in monocytes, macrophages and endothelial cells within atherosclerotic plaques. Modified citrus pectin (MCP) is produced from citrus pectin via pH and temperature modifications, which break it into shorter, non-branched, galactose-rich carbohydrate chains. MCP is able to tightly bind with galectin-3, via recognition of its carbohydrate recognition domain, and facilitates the modulation of galectin-3-induced bioactivity. The present study explored the effects of MCP on the initiation of atherosclerosis. Eight-week-old apolipoprotein E-deficient mice were treated with 1% MCP and fed an atherogenic diet for 4 weeks. The effects of MCP on atherosclerotic initiation were determined by pathological analysis and scanning electron microscope (SEM) imaging. MCP treatment reduced the size of atherosclerotic lesion areas, which was accompanied by decreased numbers of macrophages and smooth muscle cells (SMCs). Furthermore, SEM examination of the surface of the atheroma-prone vessel wall indicated that MCP treatment reduced endothelial injury. To analyze the effects of MCP on monocyte adhesion, firstly, oxidized-low density lipoprotein and various concentrations of MCP (0.025, 0.05, 0.1 and 0.25%) were incubated with the human umbilical vein endothelial cells (HUVECs) for stimulation and following this, the U937 cells were plated onto the HUVECs. The results revealed that MCP reduced the adhesion of U937 monocytes to HUVECs, indicating the adhesion-inhibiting effects of MCP. In conclusion, the present study revealed that MCP, a galectin-3 inhibitor, reduced the size of atherosclerotic lesions by inhibiting the adhesion of leucocytes to endothelial cells. Inhibition of galectin-3 function may be a therapeutic strategy for the treatment of atherosclerosis.