Statin-Induced Decrease in ATP-Binding Cassette Transporter A1 Expression via microRNA33 Induction may Counteract Cholesterol Efflux to High-Density Lipoprotein

Niesor, Eric J.; Schwartz, Gregory G.; Perez, Anne; Stauffer, Andrea; Durrwell, Alexandre; Bucklar-Suchankova, Gabriela; Benghozi, Renée; Abt, Markus; Kallend, David

doi:10.1007/s10557-015-6570-0

Cited by 61 publications

(61 citation statements)

References 32 publications

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“…49 Niesor et al even reported unfavorable properties of statins regarding HDL-facilitated cholesterol efflux. 163 Statin exposure of cholesterol-loaded human macrophages led to the upregulation of miR-33 mRNA expression, reducing both ABCA1 mRNA expression and ABCA1-mediated cholesterol efflux. 163 Interestingly, by the same mechanism, concomitant statin treatment compromised the positive effects of other HDL-raising drugs, such as the CETP-inhibitor dalcetrapib, on cholesterol efflux capacity.…”

Section: Statinsmentioning

confidence: 99%

“…163 Statin exposure of cholesterol-loaded human macrophages led to the upregulation of miR-33 mRNA expression, reducing both ABCA1 mRNA expression and ABCA1-mediated cholesterol efflux. 163 Interestingly, by the same mechanism, concomitant statin treatment compromised the positive effects of other HDL-raising drugs, such as the CETP-inhibitor dalcetrapib, on cholesterol efflux capacity. 163 Thus, one may speculate that the effects of statins on macrophage miR-33 expression interfere with the efficacy of CETP inhibitors in statin-treated patients.…”

Section: Statinsmentioning

confidence: 99%

“…163 Interestingly, by the same mechanism, concomitant statin treatment compromised the positive effects of other HDL-raising drugs, such as the CETP-inhibitor dalcetrapib, on cholesterol efflux capacity. 163 Thus, one may speculate that the effects of statins on macrophage miR-33 expression interfere with the efficacy of CETP inhibitors in statin-treated patients.…”

Section: Statinsmentioning

confidence: 99%

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Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Annema

Eckardstein

2016

Translational Research

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Low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risks of coronary heart disease. HDL mediates cholesterol efflux from macrophages for reverse transport to the liver and elicits many anti-inflammatory and anti-oxidative activities which are potentially antiatherogenic. Nevertheless, HDL has not been successfully targeted by drugs for prevention or treatment of cardiovascular diseases. One potential reason is the targeting of HDL cholesterol which does not capture the structural and functional complexity of HDL particles. Hundreds of lipid species and dozens of proteins as well as several microRNAs have been identified in HDL. This physiological heterogeneity is further increased in pathologic conditions due to additional quantitative and qualitative molecular changes of HDL components which have been associated with both loss of physiological function and gain of pathologic dysfunction. This structural and functional complexity of HDL has prevented clear assignments of molecules to the functions of normal HDL and dysfunctions of pathologic HDL. Systematic analyses of structure-function relationships of HDL-associated molecules and their modifications are needed to test the different components and functions of HDL for their relative contribution in the pathogenesis of atherosclerosis. The derived biomarkers and targets may eventually help to exploit HDL for treatment and diagnostics of cardiovascular diseases.

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Section: Statinsmentioning

confidence: 99%

Section: Statinsmentioning

confidence: 99%

Section: Statinsmentioning

confidence: 99%

See 1 more Smart Citation

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Annema

Eckardstein

2016

Translational Research

View full text Add to dashboard Cite

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“…16 Statins increase expression of miR-33 and result in inhibited ATP-binding cassette transporter (ABCA1) expression. 15,17 In J774 cells, incubation with statins, particularly simvastatin, impairs total cholesterol efflux capacity and ABCA1-specific efflux in a dose-dependent manner. 17 However, differences in total cholesterol efflux capacity and ABCA1-specific efflux capacity between near equipotent doses of other statins have been inconsistent in 2 published reports.…”

Section: Clinical Trials Hdl Cholesterol and Concomitant Use Of Higmentioning

confidence: 99%

“…15,17 In J774 cells, incubation with statins, particularly simvastatin, impairs total cholesterol efflux capacity and ABCA1-specific efflux in a dose-dependent manner. 17 However, differences in total cholesterol efflux capacity and ABCA1-specific efflux capacity between near equipotent doses of other statins have been inconsistent in 2 published reports. 15,17 These data suggest that high-intensity statin therapy may counteract the effect of HDL therapies through miR33-induced downregulation of ABCA1-mediated cholesterol efflux and provide one potential mechanism for the lack of efficacy of HDL-raising therapies in clinical trials in which all participants received statin therapy.…”

Section: Clinical Trials Hdl Cholesterol and Concomitant Use Of Higmentioning

confidence: 99%

The High-Density Lipoprotein Puzzle

Rosenson

2016

ATVB

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High-density lipoprotein (HDL) cholesterol is a robust biomarker of atherosclerotic cardiovascular disease (CVD) events. In observational studies and many clinical trials of statin therapy, HDL cholesterol levels are inversely associated with CVD events. In the Emerging Risk Factors Collaboration that included 302,430 participants enrolled in 68 long-term prospective studies, for every 15 mg/dL increase in HDL cholesterol, the hazard ratio for coronary heart disease (CHD) events was 0.71 (95% confidence interval: 0.68-0.75) in models that were stratified by sex and trial group and further adjusted for age, systolic blood pressure, smoking status, history of diabetes mellitus, and body mass index.1 These associations remained significant in models that included triglycerides and non-HDL cholesterol.Low levels of HDL cholesterol are inversely associated with apolipoprotein B-containing lipoproteins; thus, HDL cholesterol has been considered no more than a biomarker for atherogenic lipoproteins. Several studies have investigated the association between HDL cholesterol, atherogenic lipoproteins, and CVD. [2][3][4] In multivariate models that include apolipoprotein B or low-density lipoprotein (LDL) particle concentration, HDL cholesterol was not associated with increased cardiovascular risk. In the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) that included study participants with low levels of HDL cholesterol (men <45 mg/dL and women <47 mg/dL) and nonelevated triglycerides (<400 mg/dL), the risk of future CHD events was linearly associated with baseline and 6-month levels of apolipoprotein B but not with HDL cholesterol. 4 These analyses indicate that low levels of HDL cholesterol are not associated with CVD events after adjustment for atherogenic lipoprotein concentrations.

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The role and mechanism of noncoding RNAs in regulation of metabolic reprogramming in hepatocellular carcinoma

Liao

Hao

Wang

et al. 2022

Intl Journal of Cancer

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Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer.Metabolic reprogramming is considered to be an important hallmark of cancer.Emerging studies have demonstrated that noncoding RNAs (ncRNAs) are closely associated with metabolic reprogramming of HCC. NcRNAs can directly regulate the expressions or functions of metabolic enzymes or indirectly regulate the metabolism of HCC cells through some vital signaling pathways. Until now, the mechanisms of HCC development and progression remain largely unclear, and understanding the regulatory mechanism of ncRNAs on metabolic reprogramming of HCC may provide an important basis for breakthrough progress in the treatment of HCC. In this review, we summarize the ncRNAs involved in regulating metabolic reprogramming of HCC. Specifically, the regulatory roles of ncRNAs in glucose, lipid and amino acid metabolism are elaborated. In addition, we discuss the molecular mechanism of ncRNAs in regulation of metabolic reprogramming and possible therapeutic strategies that target the metabolism of cancer cells by modulating the expressions of specific ncRNAs.

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Statin-Induced Decrease in ATP-Binding Cassette Transporter A1 Expression via microRNA33 Induction may Counteract Cholesterol Efflux to High-Density Lipoprotein

Abstract: In vitro, statins increase miR33 expression, and decrease ABCA1 expression and cholesterol efflux from peripheral tissues; this may counteract the potential benefit of agents that raise HDL and apolipoprotein A-I in statin-treated patients.

Cited by 61 publications

References 32 publications

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

The High-Density Lipoprotein Puzzle

The role and mechanism of noncoding RNAs in regulation of metabolic reprogramming in hepatocellular carcinoma

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