Nuclear receptors expression chart in peripheral blood mononuclear cells identifies patients with Metabolic Syndrome

Simona D'Amore, Michele Vacca, Giusi Graziano, Andria D'Orazio, Marica Cariello, Nicola Martelli, Giuseppe Di Tullio, Roberto Salvia, Giuseppe Grandaliano, Anna Belfiore, Fabio Pellegrini, Giuseppe Palasciano, Antonio Moschetta

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Nuclear receptors are a class of 48 ligand-activated transcription factors identified as key players of metabolic and developmental processes. Most of these receptors are potential targets for pharmacological strategies in the Metabolic Syndrome. In the present study, we analyzed changes in the mRNA expression of nuclear receptors in the peripheral blood mononuclear cells of patients with Metabolic Syndrome, in order to identify novel biomarkers of disease and candidate targets for putative therapeutical approaches. Methods and results: We enrolled thirty healthy controls (14 M:16 F) and thirty naïve patients (16 M: 14 F; >3 criteria for Metabolic Syndrome upon Adult Treatment Panel III) without organ damage. Using quantitative real-time PCR, we assessed the expression patterns of nuclear receptors in peripheral blood mononuclear cells. 33/48 nuclear receptors were expressed in peripheral blood mononuclear cells. In patients with Metabolic Syndrome, we found a significant down-regulation of the entire PPAR, NR4A and RAR families, together with a repression of RXRα, VDR, and Rev-Erbα. Furthermore, we performed a novel statistical analysis with classification trees, which allowed us to depict a predictive core of nuclear receptor expression patterns characterizing subjects with Metabolic Syndrome. Random Forest Analysis identified NOR1 and PPARδ, which were both reduced in peripheral blood mononuclear cells and specifically in CD14+ cells (mostly monocytes), as classifiers of Metabolic Syndrome, with high specificity and sensitivity. Conclusions: Our results point to the use of PPAR and NR4A mRNA levels in the overall peripheral blood mononuclear cells as biomarkers of Metabolic Syndrome and bona fide putative targets of pharmacological therapy.

Original languageEnglish (US)
Pages (from-to)2289-2301
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1832
Issue number12
DOIs
StatePublished - Dec 2013

Fingerprint

Cytoplasmic and Nuclear Receptors
Blood Cells
Peroxisome Proliferator-Activated Receptors
Biomarkers
Pharmacology
Messenger RNA
Real-Time Polymerase Chain Reaction
Monocytes
Transcription Factors
Down-Regulation
Ligands
Sensitivity and Specificity
Therapeutics

Keywords

  • Epidemiology
  • Gene expression
  • Inflammation
  • Metabolic Syndrome
  • Nuclear receptors

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

Cite this

Nuclear receptors expression chart in peripheral blood mononuclear cells identifies patients with Metabolic Syndrome. / D'Amore, Simona; Vacca, Michele; Graziano, Giusi; D'Orazio, Andria; Cariello, Marica; Martelli, Nicola; Di Tullio, Giuseppe; Salvia, Roberto; Grandaliano, Giuseppe; Belfiore, Anna; Pellegrini, Fabio; Palasciano, Giuseppe; Moschetta, Antonio.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1832, No. 12, 12.2013, p. 2289-2301.

Research output: Contribution to journalArticle

D'Amore, S, Vacca, M, Graziano, G, D'Orazio, A, Cariello, M, Martelli, N, Di Tullio, G, Salvia, R, Grandaliano, G, Belfiore, A, Pellegrini, F, Palasciano, G & Moschetta, A 2013, 'Nuclear receptors expression chart in peripheral blood mononuclear cells identifies patients with Metabolic Syndrome', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1832, no. 12, pp. 2289-2301. https://doi.org/10.1016/j.bbadis.2013.09.006
D'Amore, Simona ; Vacca, Michele ; Graziano, Giusi ; D'Orazio, Andria ; Cariello, Marica ; Martelli, Nicola ; Di Tullio, Giuseppe ; Salvia, Roberto ; Grandaliano, Giuseppe ; Belfiore, Anna ; Pellegrini, Fabio ; Palasciano, Giuseppe ; Moschetta, Antonio. / Nuclear receptors expression chart in peripheral blood mononuclear cells identifies patients with Metabolic Syndrome. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2013 ; Vol. 1832, No. 12. pp. 2289-2301.
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AU - Vacca, Michele

AU - Graziano, Giusi

AU - D'Orazio, Andria

AU - Cariello, Marica

AU - Martelli, Nicola

AU - Di Tullio, Giuseppe

AU - Salvia, Roberto

AU - Grandaliano, Giuseppe

AU - Belfiore, Anna

AU - Pellegrini, Fabio

AU - Palasciano, Giuseppe

AU - Moschetta, Antonio

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N2 - Background: Nuclear receptors are a class of 48 ligand-activated transcription factors identified as key players of metabolic and developmental processes. Most of these receptors are potential targets for pharmacological strategies in the Metabolic Syndrome. In the present study, we analyzed changes in the mRNA expression of nuclear receptors in the peripheral blood mononuclear cells of patients with Metabolic Syndrome, in order to identify novel biomarkers of disease and candidate targets for putative therapeutical approaches. Methods and results: We enrolled thirty healthy controls (14 M:16 F) and thirty naïve patients (16 M: 14 F; >3 criteria for Metabolic Syndrome upon Adult Treatment Panel III) without organ damage. Using quantitative real-time PCR, we assessed the expression patterns of nuclear receptors in peripheral blood mononuclear cells. 33/48 nuclear receptors were expressed in peripheral blood mononuclear cells. In patients with Metabolic Syndrome, we found a significant down-regulation of the entire PPAR, NR4A and RAR families, together with a repression of RXRα, VDR, and Rev-Erbα. Furthermore, we performed a novel statistical analysis with classification trees, which allowed us to depict a predictive core of nuclear receptor expression patterns characterizing subjects with Metabolic Syndrome. Random Forest Analysis identified NOR1 and PPARδ, which were both reduced in peripheral blood mononuclear cells and specifically in CD14+ cells (mostly monocytes), as classifiers of Metabolic Syndrome, with high specificity and sensitivity. Conclusions: Our results point to the use of PPAR and NR4A mRNA levels in the overall peripheral blood mononuclear cells as biomarkers of Metabolic Syndrome and bona fide putative targets of pharmacological therapy.

AB - Background: Nuclear receptors are a class of 48 ligand-activated transcription factors identified as key players of metabolic and developmental processes. Most of these receptors are potential targets for pharmacological strategies in the Metabolic Syndrome. In the present study, we analyzed changes in the mRNA expression of nuclear receptors in the peripheral blood mononuclear cells of patients with Metabolic Syndrome, in order to identify novel biomarkers of disease and candidate targets for putative therapeutical approaches. Methods and results: We enrolled thirty healthy controls (14 M:16 F) and thirty naïve patients (16 M: 14 F; >3 criteria for Metabolic Syndrome upon Adult Treatment Panel III) without organ damage. Using quantitative real-time PCR, we assessed the expression patterns of nuclear receptors in peripheral blood mononuclear cells. 33/48 nuclear receptors were expressed in peripheral blood mononuclear cells. In patients with Metabolic Syndrome, we found a significant down-regulation of the entire PPAR, NR4A and RAR families, together with a repression of RXRα, VDR, and Rev-Erbα. Furthermore, we performed a novel statistical analysis with classification trees, which allowed us to depict a predictive core of nuclear receptor expression patterns characterizing subjects with Metabolic Syndrome. Random Forest Analysis identified NOR1 and PPARδ, which were both reduced in peripheral blood mononuclear cells and specifically in CD14+ cells (mostly monocytes), as classifiers of Metabolic Syndrome, with high specificity and sensitivity. Conclusions: Our results point to the use of PPAR and NR4A mRNA levels in the overall peripheral blood mononuclear cells as biomarkers of Metabolic Syndrome and bona fide putative targets of pharmacological therapy.

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