Cholesterol Efflux and Atheroprotection

Rosenson, Robert S.; Brewer, H. Bryan; Davidson, W. Sean; Fayad, Zahi A.; Fuster, Valentín; Goldstein, James; Hellerstein, Marc K.; Jiang, Xian‐Cheng; Phillips, Michael C.; Rader, Daniel J.; Remaley, Alan T.; Rothblat, George H.; Tall, Alan R.; Yvan‐Charvet, Laurent

doi:10.1161/circulationaha.111.066589

Cited by 801 publications

(501 citation statements)

References 153 publications

(175 reference statements)

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“…Interestingly, seminal studies have indicated that cholesterol efflux pathways (eg, ABCA1/ABCG1) are the novel regulators of monopoiesis, inflammation, and atherogenesis 61, 62, 63, 64, 65. Transgenic studies revealed that ABCA1/ABCG1 gene–deficient mice fed an HFD had an expanded pool of hematopoietic stem/progenitor cells, resulting in monocytosis by directly producing blood monocytes or mobilizing to the spleen and initiating extramedullary hematopoiesis 66.…”

Section: Discussionmentioning

confidence: 99%

Genetic and Pharmacologic Inhibition of the Neutrophil Elastase Inhibits Experimental Atherosclerosis

Wen

Chen

et al. 2018

JAHA

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BackgroundTo investigate whether neutrophil elastase (NE) plays a causal role in atherosclerosis, and the molecular mechanisms involved.Methods and Results NE genetic–deficient mice (Apolipoprotein E−/−/NE −/− mice), bone marrow transplantation, and a specific NE inhibitor (GW311616A) were employed in this study to establish the causal role of NE in atherosclerosis. Aortic expression of NE mRNA and plasma NE activity was significantly increased in high‐fat diet (HFD)–fed wild‐type (WT) (Apolipoprotein E−/−) mice but, as expected, not in NE‐deficient mice. Selective NE knockout markedly reduced HFD‐induced atherosclerosis and significantly increased indicators of atherosclerotic plaque stability. While plasma lipid profiles were not affected by NE deficiency, decreased levels of circulating proinflammatory cytokines and inflammatory monocytes (Ly6Chi/CD11b+) were observed in NE‐deficient mice fed with an HFD for 12 weeks as compared with WT. Bone marrow reconstitution of WT mice with NE −/− bone marrow cells significantly reduced HFD‐induced atherosclerosis, while bone marrow reconstitution of NE −/− mice with WT bone marrow cells restored the pathological features of atherosclerotic plaques induced by HFD in NE‐deficient mice. In line with these findings, pharmacological inhibition of NE in WT mice through oral administration of NE inhibitor GW311616A also significantly reduced atherosclerosis. Mechanistically, we demonstrated that NE promotes foam cell formation by increasing ATP‐binding cassette transporter ABCA1 protein degradation and inhibiting macrophage cholesterol efflux.ConclusionsWe outlined a pathogenic role for NE in foam cell formation and atherosclerosis development. Consequently, inhibition of NE may represent a potential therapeutic approach to treating cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

Genetic and Pharmacologic Inhibition of the Neutrophil Elastase Inhibits Experimental Atherosclerosis

Wen

Chen

et al. 2018

JAHA

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“…It is well known that the cholesterol is removed from macrophages within the arterial walls back into the bloodstream and out to the liver through the cholesterol-efflux pathway [83,84]. Therefore, it was assumed that measuring cholesterolefflux pathway might be a more reliable marker for CVD, compared with plasma HDL-C levels [85].…”

Section: Hdl-c Remains a Target For Therapy?mentioning

confidence: 99%

Lipids, blood pressure and kidney update 2014

Banach

Aronow

Şerban

et al. 2015

Pharmacological Research

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“…ABCA1 is widely expressed in various tissues, and mainly transfers cholesterol from peripheral tissue to pre-HDL, known as reverse cholesterol transport 31,32) . Thus, ABCA1 performs the first step of reverse cholesterol transport and prevents accumulation of an excess amount of cholesterol.…”

Section: Dyslipidemia and Transportersmentioning

confidence: 99%

“…There have been reports that a polymorphism of ABCA1 is associated with serum cholesterol levels and susceptibility to coronary heart disease [33][34][35] . Another ABC transporter (ABCG1) is also important in removing cholesterol from peripheral tissues and the formation and maturation of HDL 32,33) .…”

Section: Dyslipidemia and Transportersmentioning

confidence: 99%

Role of nutrient transporters in lifestyle-related diseases

Taketani

Yamanaka-Okumura

Yamamoto

et al. 2013

JPFSM

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Nutrient transporters play significant roles in physiological hormonal and cellular functions as well as in the maintenance of nutrient metabolism. Lifestyle-related disease can be defined as caused by a disturbance in nutrient metabolism as found in diabetes, dyslipidemia, arteriosclerosis, etc. Therefore, deterioration of nutrient transporters by a genetic mutation or abnormal regulation would cause various lifestyle-related diseases. For instance, dysregulation of muscular glucose transport causes hyperglycemia, and impairment of pancreatic glucose transport can be related to inadequate insulin secretion. These deleterious changes in glucose transport can be a cause of diabetes mellitus. Here, we introduce some examples that indicate the relationship between impairment of nutrient transporters and development of lifestylerelated diseases.

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Cholesterol Efflux and Atheroprotection

Cited by 801 publications

References 153 publications

Genetic and Pharmacologic Inhibition of the Neutrophil Elastase Inhibits Experimental Atherosclerosis

Genetic and Pharmacologic Inhibition of the Neutrophil Elastase Inhibits Experimental Atherosclerosis

Lipids, blood pressure and kidney update 2014

Role of nutrient transporters in lifestyle-related diseases

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