Overexpression of Apolipoprotein A-I Promotes Reverse Transport of Cholesterol From Macrophages to Feces In Vivo

Zhang, Yuzhen; Zanotti, Ilaria; Reilly, Muredach P.; Glick, Jane M.; Rothblat, George H.; Rader, Daniel J.

doi:10.1161/01.cir.0000086981.09834.e0

Cited by 398 publications

(347 citation statements)

References 18 publications

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“…These patterns are consistent with the thesis that cholesterol availability directly determines risk of infection, as HDL functions to transport excess cholesterol from the periphery to the liver for excretion into bile (Zhang et al 2003), hence lower HDL levels equate to less reverse cholesterol transport and organ clearance, which, in turn, could conceivably lead to an increase in the amount of cholesterol available to pathogens elsewhere in the body. Conversely, however, outside of the hospital, among men, total cholesterol is inversely related to urinary tract, venereal, musculoskeletal, and all infections and, among women, to urinary tract, all genitourinary, septicaemia, bacteraemia, miscellaneous viral site unspecified, and all infections (Iribarren et al 1998).…”

Section: Cholesterol and Infectionsupporting

confidence: 84%

Boots for Achilles: Progesterone's Reduction of Cholesterol Is a Second-Order Adaptation

Amir¹,

Fessler²

2013

The Quarterly Review of Biology

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Section: Cholesterol and Infectionsupporting

confidence: 84%

Boots for Achilles: Progesterone's Reduction of Cholesterol Is a Second-Order Adaptation

Amir¹,

Fessler²

2013

The Quarterly Review of Biology

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“…Besides HDL-C’s known ability to promote the efflux of cholesterol from cells in the arterial wall,26 and thereby maintaining cell cholesterol homeostasis, HDL-C is also antithrombotic,27 and possesses antioxidant and anti-inflammatory properties 28,29. Our HIV-infected participants had lower serum HDL-C levels and were 3.7 times more likely to have low HDL-C levels than their matched controls, while the lowest levels were seen in the nadir CD 4 cell count group.…”

Section: Discussionmentioning

confidence: 99%

Is HIV-1 infection associated with endothelial dysfunction in a population of African ancestry in South Africa?

Fourie¹,

Rooyen²,

Pieters³

et al. 2011

CardioVascular Journal of Africa

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The chronic infection status suffered by HIV-infected individuals promotes chronic arterial inflammation and injury, which leads to dysfunction of the endothelium, atherosclerosis and thrombosis. Although HIV-1 subtype C is prevalent in South Africa and accounts for almost a third of the infections worldwide, this subtype differs genetically from HIV-1 subtype B on which the majority of studies have been done. The objective of this study was to assess whether newly identified, never-treated, HIV-1-infected South African participants showed signs of endothelial dysfunction, accelerated atherosclerosis and increased blood coagulation.We compared 300 newly diagnosed (never antiretroviral-treated) HIV-infected participants to 300 age-, gender-, body mass index- and locality-matched uninfected controls. Levels of high-density lipoprotein cholesterol (HDL-C), triglycerides, interleukin-6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), fibrinogen and plasminogen activator inhibitor-1 (PAI-1), and carotid radialis pulse wave velocity (cr-PWV) were determined. The HIV-infected participants showed lower HDL-C and higher IL-6, CRP, ICAM-1 and VCAM-1 levels compared to the uninfected controls. No differences in fibrinogen and PAI-1 levels were detected. A continuous positive trend of increasing age with cr-PWV was detected in the HIV-infected group.Our findings suggest inflammatory injury of the endothelium, pointing to endothelial dysfunction of never-treated HIV-1-infected South Africans of African ancestry. Although no indication of a prothrombotic state could be detected, there was an indication of accelerated vascular aging and probable early atherosclerosis in the older HIV-infected participants.

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“…In Vivo Macrophage to Feces RCT Assay-Macrophage to feces RCT was evaluated in vivo using the assay developed by Zhang and colleagues (22), which measures transport of cholesterol from intraperitoneally injected […”

Section: Methodsmentioning

confidence: 99%

Cholesteryl Ester Transfer Protein Expression Partially Attenuates the Adverse Effects of SR-BI Receptor Deficiency on Cholesterol Metabolism and Atherosclerosis

Bouhassani

Gilibert

Moreau

et al. 2011

Journal of Biological Chemistry

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Scavenger receptor SR-BI significantly contributes to HDL cholesterol metabolism and atherogenesis in mice. However, the role of SR-BI may not be as pronounced in humans due to cholesteryl ester transfer protein (CETP) activity. To address the impact of CETP expression on the adverse effects associated with SR-BI deficiency, we cross-bred our SR-BI conditional knock-out mouse model with CETP transgenic mice. CETP almost completely restored the abnormal HDL-C distribution in SR-BI-deficient mice. However, it did not normalize the elevated plasma free to total cholesterol ratio characteristic of hepatic SR-BI deficiency. Red blood cell and platelet count abnormalities observed in mice liver deficient for SR-BI were partially restored by CETP, but the elevated erythrocyte cholesterol to phopholipid ratio remained unchanged. Complete deletion of SR-BI was associated with diminished adrenal cholesterol stores, whereas hepatic SR-BI deficiency resulted in a significant increase in adrenal gland cholesterol content. In both mouse models, CETP had no impact on adrenal cholesterol metabolism. In diet-induced atherosclerosis studies, hepatic SR-BI deficiency accelerated aortic lipid lesion formation in both CETP-expressing (4-fold) and non-CETP-expressing (8-fold) mice when compared with controls. Impaired macrophage to feces reverse cholesterol transport in mice deficient for SR-BI in liver, which was not corrected by CETP, most likely contributed by such an increase in atherosclerosis susceptibility. Finally, comparison of the atherosclerosis burden in SR-BI liver-deficient and fully deficient mice demonstrated that SR-BI exerted an atheroprotective activity in extra-hepatic tissues whether CETP was present or not. These findings support the contention that the SR-BI pathway contributes in unique ways to cholesterol metabolism and atherosclerosis susceptibility even in the presence of CETP.Epidemiological studies have demonstrated that high density lipoprotein cholesterol is a strong, independent, inverse predictor of the risk of coronary heart disease. High plasma levels of the major apolipoprotein of HDL, APOA-I, have been also shown to predict decreased risk of coronary heart disease. One major atheroprotective mechanism by which HDL/APOA-I may protect against atherosclerosis involves the transport of excess cholesterol from peripheral tissues, including macrophages, to the liver, bile, and eventually feces for excretion, a process known as reverse cholesterol transport.The scavenger receptor SR-BI is an 82-kDa glycosylated plasma membrane protein that binds HDL/APOA-I with high affinity and stimulates the bi-directional flux of cholesterol between cells and extracellular HDL particles. In mice, SR-BI, encodeed by the Scarb1 gene, is a major determinant of HDL metabolism in mice and is protective against atherosclerosis. Indeed, hepatic overexpression of SR-BI markedly reduces plasma HDL-C levels, increases biliary secretion of cholesterol, and decreases atherosclerosis (1-3), whereas deficiency of this receptor resu...

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Overexpression of Apolipoprotein A-I Promotes Reverse Transport of Cholesterol From Macrophages to Feces In Vivo

Cited by 398 publications

References 18 publications

Boots for Achilles: Progesterone's Reduction of Cholesterol Is a Second-Order Adaptation

Boots for Achilles: Progesterone's Reduction of Cholesterol Is a Second-Order Adaptation

Is HIV-1 infection associated with endothelial dysfunction in a population of African ancestry in South Africa?

Cholesteryl Ester Transfer Protein Expression Partially Attenuates the Adverse Effects of SR-BI Receptor Deficiency on Cholesterol Metabolism and Atherosclerosis

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