Potential injurious effects of the fine particulate PM2.5 on the progression of atherosclerosis in apoE-deficient mice by activating platelets and leukocytes

Abstract Dipeptyl peptidase-4 (DPP-4) inhibitors modulate the progression of atherosclerosis. To gain insights into their mechanism of action, 9-wk-old male apolipoprotein E (apoE)-deficient mice were fed a DPP-4 inhibitor, anagliptin-containing diet. The effects of anagliptin were investigated in, a monocyte cell line, human THP-1 cells, and rat smooth muscle cells (SMCs). Treatment with anagliptin for 16 wk significantly reduced accumulation of monocytes and macrophages in the vascular wall, SMC content in plaque areas, and oil red O-stained area around the aortic valve without affecting glucose tolerance or body weight. Serum DPP-4 concentrations were significantly higher in apoE-deficient mice than control mice, and the levels increased with aging, suggesting the involvement of DPP-4 in the progression of atherosclerosis. Indeed, soluble DPP-4 augmented cultured SMC proliferation, and anagliptin suppressed the proliferation by inhibiting ERK phosphorylation. In THP-1 cells, anagliptin reduced lipopolysaccharide-induced TNF-α production with inhibiting ERK phosphorylation and nuclear translocation of nuclear factor-κB. Quantitative analysis also showed that anagliptin reduced the area of atherosclerotic lesion in apoE-deficient mice. These results indicated that the anti-atherosclerotic effect of anagliptin is mediated, at least in part, through its direct inhibition of SMC proliferation and inflammatory reaction of monocytes.

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A novel thromboxane receptor antagonist and synthase inhibitor, BM-573, reduces development and progression of atherosclerosis in LDL receptor deficient mice

European Journal of Pharmacology ◽

10.1016/j.ejphar.2006.12.024 ◽

2007 ◽

Vol 561 (1-3) ◽

pp. 105-111 ◽

Cited By ~ 19

Author(s):

Tillmann Cyrus ◽

Yuemang Yao ◽

Tao Ding ◽

Jean Michel Dogné ◽

Domenico Praticò

Keyword(s):

Receptor Antagonist ◽

Ldl Receptor ◽

Thromboxane Receptor ◽

Thromboxane Receptor Antagonist ◽

Synthase Inhibitor ◽

Deficient Mice ◽

Progression Of Atherosclerosis

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Rosuvastatin inhibits MMP-2 expression and improves the progression of atherosclerosis in LDLR-deficient mice

International Journal of Cardiology ◽

10.1016/j.ijcard.2009.09.007 ◽

2009 ◽

Vol 137 ◽

pp. S2-S3

Author(s):

YONG SUN ◽

HANGYUAN GUO

Keyword(s):

Deficient Mice ◽

Progression Of Atherosclerosis

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Effect of Repetitive Glucose Spike and Hypoglycaemia on Atherosclerosis and Death Rate in Apo E-Deficient Mice

International Journal of Endocrinology ◽

10.1155/2015/406394 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Kenichi Nakajima ◽

Tomoya Mita ◽

Yusuke Osonoi ◽

Kosuke Azuma ◽

Toshiyuki Takasu ◽

...

Keyword(s):

Survival Rate ◽

Epidemiological Data ◽

Postprandial Glucose ◽

Sodium Glucose Cotransporter ◽

Apo E ◽

Potential Risk Factors ◽

Oil Red O Staining ◽

Deficient Mice ◽

Progression Of Atherosclerosis

Epidemiological data suggest that postprandial hyperglycaemia and hypoglycaemia are potential risk factors for cardiovascular disease. However, the effects of repetitive postprandial glucose spikes, repetitive hypoglycaemia, and their combination on the progression of atherosclerosis remain largely unknown. The present study investigated the effects of rapid rises and falls in glucose, and their combination, on the progression of atherosclerosis in apolipoprotein (apo) E-deficient mice. In this study, apo E-deficient mice with forced oral administration of glucose twice daily for 15 weeks were used as a model of repetitive postprandial glucose spikes, and apo E-deficient mice given an intraperitoneal injection of insulin once a week for 15 weeks were used as a model of repetitive hypoglycaemia. In addition, we established a model of both repetitive postprandial glucose spikes and hypoglycaemia by combining the above interventions. Atherosclerosis was evaluated in all mice by oil red O staining. Administration of ipragliflozin, a selective inhibitor of sodium-glucose cotransporter 2, in the mouse model of repetitive glucose spikes inhibited the progression of atherosclerosis, whereas long-term repetitive glucose spikes, repetitive hypoglycaemia, and their combination had no significant impact on atherosclerosis. However, repetitive hypoglycaemia was associated with poor survival rate. The results showed that repetitive hypoglycaemia reduces the survival rate without associated progression of atherosclerosis in apo E-deficient mice.

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Circulating autoantibodies to oxidized cardiolipin correlate with isoprostane F2α-VI levels and the extent of atherosclerosis in ApoE-deficient mice: modulation by vitamin E

Blood ◽

10.1182/blood.v97.2.459 ◽

2001 ◽

Vol 97 (2) ◽

pp. 459-464 ◽

Cited By ~ 22

Author(s):

Domenico Praticò ◽

Rajendra K. Tangirala ◽

Sohvi Hörkkö ◽

Joseph L. Witztum ◽

Wulf Palinski ◽

...

Keyword(s):

Lipid Peroxidation ◽

Vitamin E ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Antibody Titers ◽

Circulating Autoantibodies ◽

Deficient Mice ◽

Progression Of Atherosclerosis ◽

Sensitive Marker

Abstract Lipid peroxidation plays an important role in atherogenesis. Previous studies suggested that autoantibodies against epitopes of oxidized low-density lipoprotein may indicate the extent or rate of progression of atherosclerosis. The aim of this study was to investigate whether autoantibodies to oxidized phospholipids, such as oxidized cardiolipin (OxCL), correlate with levels of isoprostane F2α-VI, a sensitive marker of in vivo lipid peroxidation, as well as with the extent of atherosclerosis. Two groups of apolipoprotein E-deficient mice were fed chow with or without vitamin E (2000 IU/kg diet) for 16 weeks. In untreated animals, autoantibodies against OxCL and urinary, plasma, and aortic isoprostane F2α-VI levels increased significantly. Vitamin E treatment significantly reduced antibody titers, isoprostane levels, and atherosclerosis at the end of the study, compared with untreated mice. Autoantibodies to OxCL correlated with aortic isoprostane F2α-VI levels (r2 = 0.42,P = .001 for IgG andr2 = 0.63, P < .001 for IgM). Both aortic isoprostane F2α-VI levels (r2 = 0.59, P < .001) and titers of OxCL antibodies (r2 = 0.70, P < .001 for IgG and r2 = 0.68,P < .001 for IgM) correlated with the extent of aortic atherosclerosis. The fact that the levels of autoantibodies to OxCL correlated with a sensitive direct measure of lipid peroxidation in vivo and that both autoantibodies and aortic isoprostane F2α-VI levels correlated with the extent of atherosclerosis suggests that antibodies to OxCL are a sensitive indicator of in vivo lipid peroxidation and atherosclerosis.

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