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Gene. 2015 Oct 1;570(1):50-6. doi: 10.1016/j.gene.2015.05.074. Epub 2015 Jun 4.

Asymptomatic individuals with high HDL-C levels overexpress ABCA1 and ABCG1 and present miR-33a dysregulation in peripheral blood mononuclear cells.

Author information

1
Department of Clinical Pathology, Faculty of Medical Sciences, 126, Tessália Vieira de Camargo St., University of Campinas, Campinas, 13084-971 São Paulo, Brazil.
2
Department of Clinical Pathology, Faculty of Medical Sciences, 126, Tessália Vieira de Camargo St., University of Campinas, Campinas, 13084-971 São Paulo, Brazil. Electronic address: vanessasouzazago@gmail.com.
3
Department of Medical Genetics, Faculty of Medical Sciences, 126, Tessália Vieira de Camargo St., University of Campinas, Campinas, 13084-971 São Paulo, Brazil.
4
Department of Radiology, Faculty of Medical Sciences, 126, Tessália Vieira de Camargo St., University of Campinas, Campinas, 13084-971 São Paulo, Brazil.
5
Lipid Laboratory, Faculty of Medical Sciences, 455, Dr Arnaldo St., University of São Paulo, São Paulo, 01246-000 São Paulo, Brazil.

Abstract

Considering the growing knowledge and perspectives on microRNAs (miRNAs) that control high-density lipoprotein cholesterol (HDL-C) levels and metabolism, this study aimed at evaluating whether hsa-miR-33a and hsa-miR-128a are differentially expressed in peripheral blood mononuclear cells from asymptomatic individuals with low and high HDL-C, as well as at investigating the potential relationships with ATP binding cassete transporter A1 (ABCA1) expression, cholesterol efflux capacity and other parameters related with reverse cholesterol transport. In addition, the associations with cardiovascular risk were investigated by carotid-intima media thickness (cIMT). Asymptomatic volunteers of both genders (n=51) were classified according to HDL-C (mg/dL) in hypoalphalipoproteinemics (hypo, HDL-C ≤3 9), hyperalphalipoproteinemics (hyper, HDL-C ≥ 68) and controls (CTL, HDL-C ≥ 40<68). cIMT, lipids, lipoproteins, HDL size and volume, C reactive protein and insulin were determined, as well as the activities of several proteins and enzymes related to HDL metabolism. In a subgroup of 19 volunteers the cellular cholesterol efflux and HDL composition were determined. Total RNA was extracted from peripheral blood mononuclear cells for relative quantification experiments. Hypo volunteers presented significantly higher levels of triglycerides, VLDL-C and insulin; in addition, HDL size and volume decreased when compared with CTL and hyper. Regarding gene expression analysis, the hyper group presented a decrease of 72% in hsa-miR-33a and higher mRNA expression of ABCA1 and ABCG1 when compared with CTL. No significant differences in hsa-miR-128a expression, cholesterol efflux, cIMT or plaques were found. Further studies are necessary to elucidate the mechanisms underlying the complex miRNA network, regulating cellular cholesterol homeostasis in humans and its clinical repercussions.

KEYWORDS:

ABCA1; ABCG1; HDL; MicroRNA

PMID:
26051418
DOI:
10.1016/j.gene.2015.05.074
[Indexed for MEDLINE]

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