Repositorio
Institucional

Salazar, Luis A.

Zambrano, Tomas#Hirata, Rosario D. C.#Hirata, Mario H.#Cerda, Alvaro

Statins differentially modulate microRNAs expression in peripheral cells of hyperlipidemic subjects: A pilot study

ELSEVIER

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

en

Aim: Although statins are considered a cornerstone for the treatment of high cholesterol levels due to their powerful cholesterol-lowering effects, response to drug administration is still one of the main pitfalls of statin treatment. So far, the reasons underlying this undesired outcome are still poorly understood, but recently, various studies have suggested that miRNAs may be involved. Therefore, we aimed at evaluating the effect of short-term low-dose treatment with 2 statins on miRNAs expression in patients with hypercholesterolemia. Methods: A total of 40 hypercholesterolemic (HC) subjects following 1 month of atorvastatin (10 mg/day, n= 20) or simvastatin (10 mg/day, n= 20) were included. Multiple available boinformatic algorithms (TargetScan, miRanda, DianaLab, MicroCosm and PicTar) were employed to select miRNAs regulating genes involved in cholesterol metabolism and statin response. Differential miRNAs expression was determined in peripheral cells using the miScript (R) miRNA PCR Array platform. Pathways involving differentially expressed miRNAs were explored using the Ingenuity Pathway Analysis software. Results: Atorvastatin repressed miR-29a-3p, miR-29b-3p, miR-300, miR-33a-5p, miR-33b-5p and miR-454-3p in HC subjects. On the contrary, simvastatin did not show any effect on miRNAs expression. Network analysis indicated that atorvastatin-modulated miRNAs regulate key cholesterol genes (ABCA1, HMGCR, INSIG1, LDLR, LPL, SCAP and SREBF1). Further subgroups analyses showed that miR-106b-5p, miR-17-3p and miR-590-5p were repressed in HC subjects within the lower quartile of atorvastatin response (lower LDL-C reduction), while the expression of miR-106b-5p, miR-17-3p and miR-183-5p was higher in the upper quartile of simvastatin response (higher LDL-C reduction) (p < 0.05). Conclusion: We show that a miRNAs-mediated epigenetic mechanism is differentially affected by statins therapy in vivo, which could be implicated in the variable response to these drugs. Further studies are necessary to disclose their particular role in the cholesterol-reduction response to statins.

Artículo original

This work was supported by CNPq-Brazil (grant number 473485/2012-5), FAPESP-Brazil (grant number 2011/21967-1) and FONDECYT-Chile (grant numbers 1130675 and 1171765). Mario Hirata and Rosario Hirata are recipients of fellowships from CNPq, Brazil.

Este trabajo contó con el apoyo del CNPq-Brasil (subvención número 473485/2012-5), la FAPESP-Brasil (subvención número 2011/21967-1) y FONDECYT-Chile (subvenciones números 1130675 y 1171765). Mario Hirata y Rosario Hirata son becarios del CNPq, Brasil.

10.1016/j.ejps.2018.02.007

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Statins# microRNAs# Cholesterol# Epigenetics# Lipids

http://dx.doi.org/10.1016/j.ejps.2018.02.007

Pharmacology & Pharmacy

estatinas# microARN# Colesterol# Epigenética# lípidos

Endocrinología y Metabolismo (Incluye Diabetes, Hormonas)

Farmacología y Farmacia

Biotecnología Relacionada con la Salud

WOS:000430368800008

Statins differentially modulate microRNAs expression in peripheral cells of hyperlipidemic subjects: A pilot study

Artículo original

version publicada

ELSEVIER

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

Farmacología y farmacia

0928-0987

en

CNPq 473485/2012-5#FAPESP 2011/21967-1#ANID FONDECYT 1130675#ANID FONDECYT 1171765

CNPq 473485/2012-5

FAPESP 2011/21967-1

ANID FONDECYT 1130675

ANID FONDECYT 1171765

This work was supported by CNPq-Brazil (grant number 473485/2012-5), FAPESP-Brazil (grant number 2011/21967-1) and FONDECYT-Chile (grant numbers 1130675 and 1171765). Mario Hirata and Rosario Hirata are recipients of fellowships from CNPq, Brazil.

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