Effects of Antisense Oligonucleotides against C-Reactive Protein on the Development of Atherosclerosis in WHHL Rabbits

Yu, Qi; Liu, Zhengcao; Waqar, Ahmed Bilal; Niu, Bo; Yang, Xianghong; Shiomi, Masashi; Graham, Mark; Crooke, Rosanne M.; Liu, Enqi; Dong, Shuang; Fan, Jianglin

doi:10.1155/2014/979132

Cited by 12 publications

(17 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Blood samples were centrifuged (1,500 × g; 15 min; 4°C) to collect plasma. Plasma total cholesterol (TC), total triglycerides (TG) and high-density lipoprotein (HDL-C) were measured using a Varioskan Flash plate reader (Thermo Fisher Scientific, Inc., Waltham, MA, USA) with assay kits (BioSino Bio-Technology and Science Inc., Beijing, China) during the final week of the treatment as previously described ( 18 ). Intravenous glucose tolerance tests (IGTT) and intravenous insulin tolerance tests (IITT) were performed as previously described ( 7 ).…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA of the pancreas and liver were extracted using RNAiso Plus (Takara Bio, Inc., Otsu, Japan). RT-qPCR was performed and quantified using the 2 −ΔΔCq method as previously described ( 18 – 20 ). The sequences of the primers are listed as follows: LDLR, 5′-TGACCTTCATCCCAGAGCCTTC-3′ and 5′-GGCATGAGCGGGTATCCATC-3′; proprotein convertase subtilisin/kexin type 9 (PCSK9), 5′-TATCCCAGCATGGCACCAGA-3′ and 5′-ATGGTGACCCTGCCCTCAA-3′; sterol regulatory element-binding protein 2 (SREBP-2), 5′-CCCTTGACTTCCTTGCTGCA-3′ and 5′-GCGTGAGTGTGGGCGAATC-3′; E3 ubiquitin-protein ligase MYLIP (IDOL), 5′-AGGAGATCAACTCCACCTTCTG-3′ and 5′-ATCTGCAGACCGGACAGG-3; GAPDH, 5′-ACTGAGGACCAGGTTGTC-3′ and 5′-TGCTGTAGCCGTATTCATTG-3′.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Short‑term use of atorvastatin affects glucose homeostasis and suppresses the expression of LDL receptors in the pancreas of mice

Wang

Meng

et al. 2018

Mol Med Report

Self Cite

View full text Add to dashboard Cite

Low-density lipoprotein receptors (LDLRs) may serve a role in the diabetogenic effect of statins; however, the effects of statins on LDLR expression and its regulation in the pancreas and islets have yet to be determined. To exclude the long-term effects of treatment with atorvastatin, which allows mice to adapt, male C57BL/j and apolipoprotein E-deficient mice were acutely treated with oral atorvastatin for 6 weeks, and glucose homeostasis and LDLR expression in the pancreas and islets were examined. In the present study, it was observed that the short-term use of atorvastatin affected insulin sensitivity in normal mice and glucose tolerance in hyperlipidemic mice. Furthermore, it was identified that 6 weeks of treatment with atorvastatin suppressed LDLR expression in the pancreas and pancreatic islets in C57BL/j mice, and an increase in proprotein convertase subtilisin/kexin type 9 expression was additionally observed in the pancreas. However, 6 weeks of treatment with atorvastatin did not affect LDLR expression in the pancreas of hyperlipidemic mice. It may be concluded that the short-term use of atorvastatin disturbs glucose homeostasis and suppresses LDLR expression in the pancreas and pancreatic islets in C57BL/j mice, suggesting that the role of LDLR in the diabetogenic effect of statins requires further investigation.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Short‑term use of atorvastatin affects glucose homeostasis and suppresses the expression of LDL receptors in the pancreas of mice

Wang

Meng

et al. 2018

Mol Med Report

Self Cite

View full text Add to dashboard Cite

show abstract

“…Compared with wild-type rabbits, transgenic rabbits expressing human CRP developed similar atherosclerotic lesions on a cholesterol-rich diet 89 . Regarding loss-of-function studies, CRP-deficient mice displayed either equivalent or actually increased atherosclerotic lesions compared with controls 90 , and whereas CRP antisense oligonucleotides effectively lowered plasma CRP levels in Watanabe heritable hyperlipidemic rabbits, they did not impact atherosclerosis in the rabbits 91 . Recognizing that SAP is the acute phase reactant and CRP equivalent in mice, SAP concentrations have been measured during the development of atherosclerosis in apoE −/− mice, and they were found to be unchanged 84,85 .…”

Section: Fcγ Receptors Ligands and Cvd In Animal Modelsmentioning

confidence: 97%

Fcγ Receptors and Ligands and Cardiovascular Disease

Tanigaki

Sundgren

Khera

et al. 2015

Circulation Research

View full text Add to dashboard Cite

Fcγ receptors (FcγR) classically modulate intracellular signaling upon binding of the Fc region of IgG in immune response cells. How FcγR and their ligands impact cardiovascular health and disease has recently been interrogated in both preclinical and clinical studies. The stimulation of activating FcγR in endothelial cells, vascular smooth muscle cells and monocytes/macrophages causes a variety of cellular responses that may contribute to vascular disease pathogenesis. Stimulation of the lone inhibitory FγcR, FcγRIIB, also has adverse consequences in endothelial cells, antagonizing NO production and reparative mechanisms. In preclinical disease models, activating FcγR promote atherosclerosis whereas FcγRIIB is protective, and activating FcγR also enhance thrombotic and non-thrombotic vascular occlusion. The FcγR ligand C-reactive protein (CRP) has undergone intense study. Although in rodents CRP does not impact atherosclerosis, it causes hypertension and insulin resistance and worsens myocardial infarction. Massive data has accumulated indicating an association between increases in circulating CRP and coronary heart disease in humans. However, Mendelian randomization studies reveal that CRP is not likely a disease mediator. CRP genetics and hypertension warrants further investigation. Studies to date of genetic variants of activating FcγR are insufficient to implicate the receptors in coronary heart disease pathogenesis in humans. However, a link between FcγRIIB and human hypertension may be emerging. Further knowledge of the vascular biology of FcγR and their ligands will potentially enhance our understanding of cardiovascular disorders, particularly in patients whose greater predisposition for disease is not explained by traditional risk factors, such as individuals with autoimmune disorders.

show abstract

“…After formalin fixation, the whole aortas were stained with Sudan IV and photographed for the evaluation of the gross size of atherosclerotic lesions. For histological analysis, the aortic arch of each rabbit was cut into cross 8 to 10 sections (4 µm) as previously described (Yu et al 2014). All sections D r a f t were stained with Hematoxylin and Eosin (H&E) and Elastica van Gieson (EVG) and immunohistochemically stained with RAM11 antibody against macrophages (dilution 1:200; Dako Inc., CA, USA) and smooth muscle α-actin (dilution 1:200; Thermo Fisher Scientific Inc., CA, USA).…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Dietary restriction slightly affects glucose homeostasis and delays plasma cholesterol removal in rabbits with dietary lipid lowering

Liu

Zhang

et al. 2018

Appl. Physiol. Nutr. Metab.

Self Cite

View full text Add to dashboard Cite

Dietary restriction (DR) has been reported to have beneficial effects on atherosclerotic progression as well as lipid and glucose metabolism, but little is known about whether these effects can be enhanced or weakened by dietary lipid lowering. Here, after 12 weeks of high-cholesterol diet feeding, hypercholesterolemic rabbits were fed with either a standard chow diet ad libitum (AL) or a standard chow diet with DR for 16 weeks of dietary lipid lowering. We found that the DR group exhibited a loss of body weight, smaller internal organs, and reduced fat mass, while the AL group accumulated more subcutaneous fat than the baseline group. DR treatment slightly worsened glucose tolerance but enhanced insulin sensitivity, and a slight effect of DR on insulin secretion was also observed. After dietary cholesterol withdrawal, rabbits showed persistent lowering of total cholesterol and triglycerides in plasma. However, the DR group had significantly higher plasma total cholesterol than the AL group at most time points during weeks 7 to 16 of lipid lowering. Although both the AL and DR groups developed more severe atherosclerosis than the baseline group, DR did not improve atherosclerotic progression or the accumulation of macrophages and smooth muscle cells. We conclude that DR affected glucose and lipid metabolism but did not ameliorate atherosclerosis in rabbits when associated with lipid lowering by dietary cholesterol withdrawal.

show abstract

Effects of Antisense Oligonucleotides against C-Reactive Protein on the Development of Atherosclerosis in WHHL Rabbits

Cited by 12 publications

References 34 publications

Short‑term use of atorvastatin affects glucose homeostasis and suppresses the expression of LDL receptors in the pancreas of mice

Short‑term use of atorvastatin affects glucose homeostasis and suppresses the expression of LDL receptors in the pancreas of mice

Fcγ Receptors and Ligands and Cardiovascular Disease

Dietary restriction slightly affects glucose homeostasis and delays plasma cholesterol removal in rabbits with dietary lipid lowering

Contact Info

Product

Resources

About