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C-reactive protein/oxidised low-density lipoprotein/β2-glycoprotein I complex promotes atherosclerosis in diabetic BALB/c mice via p38mitogen-activated protein kinase signal pathway.

Zhang R, Zhou SJ, Li CJ, Wang XN, Tang YZ, Chen R, Lv L, Zhao Q, Xing QL, Yu DM, Yu P - Lipids Health Dis (2013)

Bottom Line: The mRNA expressions of receptors associated with lipid metabolism were quantified by real-time PCR.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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Diabetic Nephropathy Hemodialysis, Key Laboratory of Hormones and Development, Ministry of Health, Metabolic Diseases Hospital & Tianjin Institute of Endocrinology Tianjin Medical University, Tongan Street, Tianjin, Heping District 300070, China.

ABSTRACT

Background: 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.

Methods: BALB/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.

Results: The 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).

Conclusions: CRP/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.

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Plasma lipid level of the DM group significantly increased. *P < 0.05, compared to group NC.
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Figure 2: Plasma lipid level of the DM group significantly increased. *P < 0.05, compared to group NC.

Mentions: Plasma triglycerol (TG) and total cholesterol (TC) levels were higher in DM group than in NC group. The TC levels of oxLDL, CRP/oxLDL/β2GPI, and PBS groups were higher than those of NC group (P< 0.05), whereas the TG level did not exhibit significant difference in all the DM groups (Figure 2). The β2GPI and oxLDL/β2GPI groups showed decreased levels of plasma TG and TC.


C-reactive protein/oxidised low-density lipoprotein/β2-glycoprotein I complex promotes atherosclerosis in diabetic BALB/c mice via p38mitogen-activated protein kinase signal pathway.

Zhang R, Zhou SJ, Li CJ, Wang XN, Tang YZ, Chen R, Lv L, Zhao Q, Xing QL, Yu DM, Yu P - Lipids Health Dis (2013)

Plasma lipid level of the DM group significantly increased. *P < 0.05, compared to group NC.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643870&req=5

Figure 2: Plasma lipid level of the DM group significantly increased. *P < 0.05, compared to group NC.
Mentions: Plasma triglycerol (TG) and total cholesterol (TC) levels were higher in DM group than in NC group. The TC levels of oxLDL, CRP/oxLDL/β2GPI, and PBS groups were higher than those of NC group (P< 0.05), whereas the TG level did not exhibit significant difference in all the DM groups (Figure 2). The β2GPI and oxLDL/β2GPI groups showed decreased levels of plasma TG and TC.

Bottom Line: The mRNA expressions of receptors associated with lipid metabolism were quantified by real-time PCR.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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Diabetic Nephropathy Hemodialysis, Key Laboratory of Hormones and Development, Ministry of Health, Metabolic Diseases Hospital & Tianjin Institute of Endocrinology Tianjin Medical University, Tongan Street, Tianjin, Heping District 300070, China.

ABSTRACT

Background: 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.

Methods: BALB/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.

Results: The 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).

Conclusions: CRP/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.

Show MeSH
Related in: MedlinePlus