Adenosine Monophosphate-activated Protein Kinase Induces Cholesterol Efflux from Macrophage-derived Foam Cells and Alleviates Atherosclerosis in Apolipoprotein E-deficient Mice*

Li, Dan; Wang, Duan; Wang, Yun; Liu, Wenhua; Feng, Xiaodong; Xia, Min

doi:10.1074/jbc.m110.159772

Cited by 108 publications

(84 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Expression of ABCA1 protein in tissues of STZ-induced diabetic rats ABCA1 is the rate-controlling transporter in reverse cholesterol transport, which plays the most important role in the maintenance of cellular cholesterol homeostasis [16,17] . To investigate whether the alteration in cholesterol in the tissues of diabetic rats came from a change in ABCA1 expression, the levels of the ABCA1 protein in the tissues were measured using western blot analysis.…”

Section: Resultsmentioning

confidence: 99%

Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

Wang

Liu

et al. 2012

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: Diabetes is associated with elevated serum total cholesterol level and disrupted lipoprotein subfractions. The aim of this study was to examine alterations in the tissue cholesterol contents closely related to diabetic complications. Methods: Intraperitoneal injection of streptozotocin was used to induce type 1 diabetes in adult male Sprague-Dawley rats. On d 35 after the injection, liver, heart, intestine, kidney, pancreas, cerebral cortex and hippocampus were isolated from the rats. The content of total and free cholesterol in the tissues was determined using HPLC. The ATP-binding cassette protein A1 (ABCA1) protein and ApoE mRNA were measured using Western blot and QT-PCR analyses, respectively. Results: In diabetic rats, the level of free cholesterol was significantly decreased in the peripheral tissues, but significantly elevated in hippocampus, as compared with those in the control rats. Diabetic rats showed a trend of decreasing the total cholesterol level in the peripheral tissues, but significant change was only found in kidney and liver. In diabetic rats, the level of the ABCA1 protein was significantly increased in the peripheral tissues and cerebral cortex; the expression of ApoE mRNA was slightly decreased in hippocampus and cerebral cortex, but the change had no statistical significance. Conclusion: Type 1 diabetes decreases the free cholesterol content in the peripheral tissues and increases the free cholesterol content in hippocampus. The decreased free cholesterol level in the peripheral tissues may be partly due to the increased expression of the ABCA1 protein.

show abstract

Section: Resultsmentioning

confidence: 99%

Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

Wang

Liu

et al. 2012

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…In addition to the beneficial effects of AMPK in the endothelium, activation of AMPK by the pharmacological activator aminoimidazole-carboxamideribonucleotide (AICAR) profoundly inhibited platelet-derived growth factoror angiotensin II-induced smooth muscle cell proliferation (42). In addition, AICAR inhibited the formation of foam cells and progression of atherosclerosis (43). In contrast, genetic deletion of AMPKα2 aggravated the progression of atherosclerosis in ApoE -/-mice (44).…”

Section: A M P K I N T R P V 1 -M E D I a T E D E N O S A C T I Vmentioning

confidence: 99%

Implication of AMP-Activated Protein Kinase in Transient Receptor Potential Vanilloid Type 1-Mediated Activation of Endothelial Nitric Oxide Synthase

Ching

Chen

et al. 2012

Mol Med

View full text Add to dashboard Cite

We investigated whether AMP-activated protein kinase (AMPK), a multifunctional regulator of energy homeostasis, is involved in transient receptor potential vanilloid type 1 (TRPV1)-mediated activation of endothelial nitric oxide synthase (eNOS) in endothelial cells (ECs) and mice. In ECs, treatment with evodiamine, the activator of TRPV1, increased the phosphorylation of AMPK, acetyl-CoA carboxylase (ACC) and eNOS, as revealed by Western blot analysis. Inhibition of AMPK activation by compound C or dominant-negative AMPK mutant abrogated the evodiamine-induced increase in phosphorylation of AMPK and eNOS and NO bioavailability, as well as tube formation in ECs. Immunoprecipitation and two-hybrid analysis demonstrated that AMPK mediated the evodiamine-induced increase in the formation of a TRPV1-eNOS complex. Additionally, TRPV1 activation by evodiamine increased the phosphorylation of AMPK and eNOS in aortas of wild-type mice but did not activate eNOS in aortas of TRPV1-deficient mice. In mice, inhibition of AMPK activation by compound C markedly decreased evodiamine-evoked angiogenesis in matrigel plugs and in a hind-limb ischemia model. Moreover, evodiamine-induced phosphorylation of AMPK and eNOS in aortas of apolipoprotein E-deficient (ApoE -/-) mice was abrogated in TRPV1-deficient ApoE -/-mice. In conclusion, TRPV1 activation may trigger AMPK-dependent signaling, which leads to enhanced activation of AMPK and eNOS and retarded development of atherosclerosis.

show abstract

“…Both WT and ApoE / mice were randomly divided into two groups (n 6 mice per group), normal diet (ND) and high-fat diet (HFD; 15.8% fat and 1.25% cholesterol) for 8 weeks, as previously described 16) . Then, peritoneal macrophages were harvested from ApoE / mice and C57BL/6 mice, as previously described 26,27) . All experiments were conducted in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and with approval of the Shanghai Jiao Tong University (Shanghai, China) Animal Experiments Ethics Committee.…”

Section: Animal Studiesmentioning

confidence: 99%

UFM1 Protects Macrophages from oxLDL-Induced Foam Cell Formation Through a Liver X Receptor α Dependent Pathway

Pang

Xiong

et al. 2015

J Atheroscler Thromb

View full text Add to dashboard Cite

Aim: Macrophage foam cell formation is the most prominent characteristic of the early stages of atherosclerosis. Ubiquitin Fold Modifier 1 (UFM1) is a new member of the ubiquitin-like protein family, and its underlying mechanism of action in macrophage foam cell formation is poorly understood. Our current study focuses on UFM1 and investigates its role in macrophage foam cell formation. Methods: Using real-time quantitative PCR (qRT-PCR) and western blot analysis, we first analyzed the UFM1 expression in mouse peritoneal macrophages (MPMs) from ApoE / mice in vivo and in human macrophages treated with oxLDL in vitro. Subsequently, the effects of UFM1 on macrophages foam cell formation were determined by Nile Red staining and direct lipid analysis. We then examined whether UFM1 affects the process of lipid metabolism in macrophages. Lastly, with the method of small interfering RNA (siRNA), we delineated the mechanism of UFM1 to attenuate lipid accumulation in THP-1 macrophages. Results: UFM1 is dramatically upregulated under atherosclerosis conditions both in vivo and in vitro. Moreover, UFM1 markedly decreased macrophage foam cell formation. Mechanistic studies revealed that UFM1 increased the macrophage cholesterol efflux, which was due to the increased expression of ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1). Furthermore, the upregulation of ABCA1 and ABCG1 by UFM1 resulted from liver X receptor (LXR ) activation, which was confirmed by the observation that LXR siRNA prevented the expression of ABCA1 and ABCG1. Consistent with this, the UFM1-mediated attenuation of lipid accumulation was abolished by such inhibition. Conclusions: Taken together, our results showed that UFM1 could suppress foam cell formation via the LXR -dependent pathway.

show abstract

Adenosine Monophosphate-activated Protein Kinase Induces Cholesterol Efflux from Macrophage-derived Foam Cells and Alleviates Atherosclerosis in Apolipoprotein E-deficient Mice*

Cited by 108 publications

References 53 publications

Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

Implication of AMP-Activated Protein Kinase in Transient Receptor Potential Vanilloid Type 1-Mediated Activation of Endothelial Nitric Oxide Synthase

UFM1 Protects Macrophages from oxLDL-Induced Foam Cell Formation Through a Liver X Receptor α Dependent Pathway

Contact Info

Product

Resources

About