Identification of miR-9-5p as direct regulator of ABCA1 and HDL-driven reverse cholesterol transport in circulating CD14 + cells of patients with metabolic syndrome

Simona D'Amore, Jennifer Härdfeldt, Marica Cariello, Giusi Graziano, Massimiliano Copetti, Giuseppe Di Tullio, Marilidia Piglionica, Natasha Scialpi, Carlo Sabbà, Giuseppe Palasciano, Michele Vacca, Antonio Moschetta

Research output: Contribution to journalArticle

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Abstract

Aims Metabolic syndrome (MS) is a cluster of cardio-metabolic risk factors associated with atherosclerosis and low-grade inflammation. Using unbiased expression screenings in peripheral blood mononuclear cells, we depict here a novel expression chart of 678 genes and 84 microRNAs (miRNAs) controlling inflammatory, immune and metabolic responses. In order to further elucidate the link between inflammation and the HDL cholesterol pathway in MS, we focussed on the regulation of the ATP-binding cassette transporter A1 (ABCA1), a key player in cholesterol efflux (CE). Methods and results ABCA1 mRNA levels are suppressed in CD14 + cells of MS patients and are negatively correlated to body mass index (BMI), insulin-resistance (HOMA-IR) and cardiovascular risk, and positively to HDL cholesterol and CE. miRNA target in silico prediction identified a putative modulatory role of ABCA1 for the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-B) target miR-9-5p, whose expression pattern was up-regulated in CD14 + cells of MS patients, positively correlated to BMI, HOMA-IR, and triglycerides, and negatively to ABCA1 mRNA levels, HDL cholesterol and CE. Ectopic gain and loss of miR-9-5p function in macrophages modulated ABCA1 mRNA and protein levels, ABCA1 miRNA 3'-untranslated region target sequence reporter assay, and CE into HDL, thus confirming ABCA1 as a target of miR-9-5p. Conclusions We identified the NF-B target miR-9-5p as a negative regulator of ABCA1 adding a novel target pathway in the relationship between inflammation and HDL-driven reverse cholesterol transport for prevention or treatment of atherosclerosis in MS.

Original languageEnglish
Pages (from-to)1154-1164
Number of pages11
JournalCardiovascular Research
Volume114
Issue number8
DOIs
Publication statusPublished - Jul 1 2018

Fingerprint

ATP-Binding Cassette Transporters
Cholesterol
MicroRNAs
HDL Cholesterol
Inflammation
Messenger RNA
Atherosclerosis
Body Mass Index
3' Untranslated Regions
Metabolic Networks and Pathways
Computer Simulation
Insulin Resistance
Blood Cells
Triglycerides
B-Lymphocytes
Macrophages
Light

Keywords

  • ABCA1
  • Gene and miRNA expression
  • HDL cholesterol
  • Metabolic syndrome
  • Reverse cholesterol transport

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Identification of miR-9-5p as direct regulator of ABCA1 and HDL-driven reverse cholesterol transport in circulating CD14 + cells of patients with metabolic syndrome. / D'Amore, Simona; Härdfeldt, Jennifer; Cariello, Marica; Graziano, Giusi; Copetti, Massimiliano; Di Tullio, Giuseppe; Piglionica, Marilidia; Scialpi, Natasha; Sabbà, Carlo; Palasciano, Giuseppe; Vacca, Michele; Moschetta, Antonio.

In: Cardiovascular Research, Vol. 114, No. 8, 01.07.2018, p. 1154-1164.

Research output: Contribution to journalArticle

D'Amore, S, Härdfeldt, J, Cariello, M, Graziano, G, Copetti, M, Di Tullio, G, Piglionica, M, Scialpi, N, Sabbà, C, Palasciano, G, Vacca, M & Moschetta, A 2018, 'Identification of miR-9-5p as direct regulator of ABCA1 and HDL-driven reverse cholesterol transport in circulating CD14 + cells of patients with metabolic syndrome', Cardiovascular Research, vol. 114, no. 8, pp. 1154-1164. https://doi.org/10.1093/cvr/cvy077
D'Amore, Simona ; Härdfeldt, Jennifer ; Cariello, Marica ; Graziano, Giusi ; Copetti, Massimiliano ; Di Tullio, Giuseppe ; Piglionica, Marilidia ; Scialpi, Natasha ; Sabbà, Carlo ; Palasciano, Giuseppe ; Vacca, Michele ; Moschetta, Antonio. / Identification of miR-9-5p as direct regulator of ABCA1 and HDL-driven reverse cholesterol transport in circulating CD14 + cells of patients with metabolic syndrome. In: Cardiovascular Research. 2018 ; Vol. 114, No. 8. pp. 1154-1164.
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abstract = "Aims Metabolic syndrome (MS) is a cluster of cardio-metabolic risk factors associated with atherosclerosis and low-grade inflammation. Using unbiased expression screenings in peripheral blood mononuclear cells, we depict here a novel expression chart of 678 genes and 84 microRNAs (miRNAs) controlling inflammatory, immune and metabolic responses. In order to further elucidate the link between inflammation and the HDL cholesterol pathway in MS, we focussed on the regulation of the ATP-binding cassette transporter A1 (ABCA1), a key player in cholesterol efflux (CE). Methods and results ABCA1 mRNA levels are suppressed in CD14 + cells of MS patients and are negatively correlated to body mass index (BMI), insulin-resistance (HOMA-IR) and cardiovascular risk, and positively to HDL cholesterol and CE. miRNA target in silico prediction identified a putative modulatory role of ABCA1 for the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-B) target miR-9-5p, whose expression pattern was up-regulated in CD14 + cells of MS patients, positively correlated to BMI, HOMA-IR, and triglycerides, and negatively to ABCA1 mRNA levels, HDL cholesterol and CE. Ectopic gain and loss of miR-9-5p function in macrophages modulated ABCA1 mRNA and protein levels, ABCA1 miRNA 3'-untranslated region target sequence reporter assay, and CE into HDL, thus confirming ABCA1 as a target of miR-9-5p. Conclusions We identified the NF-B target miR-9-5p as a negative regulator of ABCA1 adding a novel target pathway in the relationship between inflammation and HDL-driven reverse cholesterol transport for prevention or treatment of atherosclerosis in MS.",
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T1 - Identification of miR-9-5p as direct regulator of ABCA1 and HDL-driven reverse cholesterol transport in circulating CD14 + cells of patients with metabolic syndrome

AU - D'Amore, Simona

AU - Härdfeldt, Jennifer

AU - Cariello, Marica

AU - Graziano, Giusi

AU - Copetti, Massimiliano

AU - Di Tullio, Giuseppe

AU - Piglionica, Marilidia

AU - Scialpi, Natasha

AU - Sabbà, Carlo

AU - Palasciano, Giuseppe

AU - Vacca, Michele

AU - Moschetta, Antonio

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Aims Metabolic syndrome (MS) is a cluster of cardio-metabolic risk factors associated with atherosclerosis and low-grade inflammation. Using unbiased expression screenings in peripheral blood mononuclear cells, we depict here a novel expression chart of 678 genes and 84 microRNAs (miRNAs) controlling inflammatory, immune and metabolic responses. In order to further elucidate the link between inflammation and the HDL cholesterol pathway in MS, we focussed on the regulation of the ATP-binding cassette transporter A1 (ABCA1), a key player in cholesterol efflux (CE). Methods and results ABCA1 mRNA levels are suppressed in CD14 + cells of MS patients and are negatively correlated to body mass index (BMI), insulin-resistance (HOMA-IR) and cardiovascular risk, and positively to HDL cholesterol and CE. miRNA target in silico prediction identified a putative modulatory role of ABCA1 for the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-B) target miR-9-5p, whose expression pattern was up-regulated in CD14 + cells of MS patients, positively correlated to BMI, HOMA-IR, and triglycerides, and negatively to ABCA1 mRNA levels, HDL cholesterol and CE. Ectopic gain and loss of miR-9-5p function in macrophages modulated ABCA1 mRNA and protein levels, ABCA1 miRNA 3'-untranslated region target sequence reporter assay, and CE into HDL, thus confirming ABCA1 as a target of miR-9-5p. Conclusions We identified the NF-B target miR-9-5p as a negative regulator of ABCA1 adding a novel target pathway in the relationship between inflammation and HDL-driven reverse cholesterol transport for prevention or treatment of atherosclerosis in MS.

AB - Aims Metabolic syndrome (MS) is a cluster of cardio-metabolic risk factors associated with atherosclerosis and low-grade inflammation. Using unbiased expression screenings in peripheral blood mononuclear cells, we depict here a novel expression chart of 678 genes and 84 microRNAs (miRNAs) controlling inflammatory, immune and metabolic responses. In order to further elucidate the link between inflammation and the HDL cholesterol pathway in MS, we focussed on the regulation of the ATP-binding cassette transporter A1 (ABCA1), a key player in cholesterol efflux (CE). Methods and results ABCA1 mRNA levels are suppressed in CD14 + cells of MS patients and are negatively correlated to body mass index (BMI), insulin-resistance (HOMA-IR) and cardiovascular risk, and positively to HDL cholesterol and CE. miRNA target in silico prediction identified a putative modulatory role of ABCA1 for the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-B) target miR-9-5p, whose expression pattern was up-regulated in CD14 + cells of MS patients, positively correlated to BMI, HOMA-IR, and triglycerides, and negatively to ABCA1 mRNA levels, HDL cholesterol and CE. Ectopic gain and loss of miR-9-5p function in macrophages modulated ABCA1 mRNA and protein levels, ABCA1 miRNA 3'-untranslated region target sequence reporter assay, and CE into HDL, thus confirming ABCA1 as a target of miR-9-5p. Conclusions We identified the NF-B target miR-9-5p as a negative regulator of ABCA1 adding a novel target pathway in the relationship between inflammation and HDL-driven reverse cholesterol transport for prevention or treatment of atherosclerosis in MS.

KW - ABCA1

KW - Gene and miRNA expression

KW - HDL cholesterol

KW - Metabolic syndrome

KW - Reverse cholesterol transport

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