Effects of platelet microparticles on atherosclerotic plaque formation and stability in ApoE-/- mice

Abstract

Objective To investigate the effect of platelet microparticles (PMPs) from C57BL/6 mice on atherosclerotic plaque formation and plaque stability in apolipoprotein E knockout (ApoE-/-) mice. Methods Forty ApoE-/- mice (8 weeks old) were fed with a high-fat diet for 4 weeks and subsequently randomized into 4 equal groups for intravenous (through the tail vein) injections of PBS (PBS group), PMPs-free supernatant (SUP group), low-dose PMPs (LDP group, 1×107), or high-dose PMPs (HDP group, 3×107) once a week for 8 weeks. At the end of the experiment, the mice were euthanized and the blood samples were collected for analysis of blood routine, blood lipids, liver and kidney functions and inflammatory factors including C-reactive protein (CRP), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). The aorta and brachiocephalic trunk were sampled to detect atherosclerotic plaque formation. Oil Red O staining, HE staining, Masson staining and immunohistochemistry were used to examine the stability of the atherosclerotic plaques. Results The 4 groups of mice showed no significant differences in body weight, blood routine (WBC, RBC, PLT, HGB), blood lipids (TG, TCH, LDL, and HDL), liver (ALT and AST) or kidney (UN and Cr) functions, but the serum levels of CRP, IL-1β and TNF-α were significantly higher in LDP and HDP groups than in PBS and SUP groups (P < 0.05). The total area of aortic atherosclerotic plaques were significantly greater in LDP and HDP groups than in the other 2 groups (P < 0.05). Compared with the PBS group, all the other 3 groups showed significantly increased lipid cores in the plaques (P < 0.05). The content of collagen and the number of smooth muscle cells in the plaques were significantly lower while the number of macrophages in the plaques were significantly greater in HDP group than in PBS group (P < 0.05). Conclusion In ApoE-/- mice with high-fat feeding, treatment with PMPs promotes atherosclerotic plaque formation, increases macrophage infiltration and inflammation and reduces collagen content and the number of smooth muscle cells in the plaques, leading thus to a decreased plaque stability.

Keywords

• platelet microparticles
• apolipoprotein e knockout mice
• atherosclerosis
• plaque stability