Abstract
BackgroundThe aim of this study was to investigate the effect of C-reactive protein/oxidised low-density lipoprotein/β2-glycoprotein I (CRP/oxLDL/β2GPI) complex on atherosclerosis (AS) in diabetic BALB/c mice.MethodsBALB/c mice were fed high-fat and normal diet. Eight weeks later, the mice fed with high-fat diet were injected with streptozotocin (STZ) to induce diabetes. The diabetic mice were respectively injected twice monthly with 20 μg oxLDL, 20 μg β2GPI, 40 μg oxLDL/β2GPI complex, 44 μg CRP/oxLDL/β2GPI complex, and PBS. Aortas were stained with Sudan IV to investigate lipid plaque formation. The infiltration condition of smooth muscle cells (SMCs), macrophages, and T cells in the aortas were determined by immunohistochemistry (IH). The mRNA expressions of receptors associated with lipid metabolism were quantified by real-time PCR. The phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and MKK3/6 in aorta tissues were assessed by Western blot. The expression of inflammation cytokines was evaluated by protein chip.ResultsThe lipid plaques were more extensive, the lumen area was obviously narrower, the ratio of intima and media thickness were increased, and the normal internal elastic lamia structure and endothelial cell disappeared (P < 0.05) in the oxLDL and CRP/oxLDL/β2GPI groups (P < 0.05). CRP/oxLDL/β2GPI complex dramatically promoted infiltration of SMCs, macrophages, and T cells, improved the mRNA expression of ABCA1 and ABCG1, but reduced the mRNA expression of SR-BI and CD36 and increased the phosphorylation of p38MAPK and MKK3/6 (all P < 0.05). The highest expression levels of IL-1, IL-9, PF-4, bFGF, and IGF-II were detected in the CRP/oxLDL/β2GPI group (P < 0.05).ConclusionsCRP/oxLDL/β2GPI complex aggravated AS in diabetic BALB/c mice by increasing lipid uptake, the mechanism of which may be mediated by the p38MAPK signal pathway.
Highlights
The aim of this study was to investigate the effect of C-reactive protein/oxidised low-density lipoprotein/β2-glycoprotein I (CRP/oxidised low density lipoprotein (oxLDL)/β2GPI) complex on atherosclerosis (AS) in diabetic BALB/c mice
Β2GPI interacts with oxidised low density lipoprotein via 7-ketocholesterol having an w-carboxyl acyl chain, producing stable and nondissociable oxLDL/β2GPI complexes [5], which could further interacts with C-reactive protein (CRP), producing CRP/oxLDL/β2GPI complex [6]
Plasma lipid level of diabetic BALB/c mice Plasma triglycerol (TG) and total cholesterol (TC) levels were higher in DM group than in NC group
Summary
The aim of this study was to investigate the effect of C-reactive protein/oxidised low-density lipoprotein/β2-glycoprotein I (CRP/oxLDL/β2GPI) complex on atherosclerosis (AS) in diabetic BALB/c mice. Research has demonstrated that the levels of oxLDL/β2GPI and CRP/oxLDL/β2GPI complexes in the serum of diabetic patients were obviously higher than those of the normal control [6]. The amounts of these complexes have been found in AS plaque tissues using immunohistochemistry, indicating that β2GPI complexes have an important function in AS development [6,7]. This study further explored the effect of CRP/oxLDL/β2GPI complex on AS occurrence and on the development of diabetic mice through in vivo research and the possible pathogenic mechanism
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