Role of statins on modulation of microRNAs in mononuclear cells from hypercholesterolemic patients

• Grant number: 11/21967-1
• Support type: Regular Research Grants
• Duration: July 01, 2012 - June 30, 2014
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Rosario Dominguez Crespo Hirata
• Grantee: Rosario Dominguez Crespo Hirata
• Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Assoc. researchers: Glauber da Costa de Brito ; Luis Antonio Salazar Navarrete ; Mario Hiroyuki Hirata

Abstract

Cardiovascular disease (CVD) is considered the main cause of mortality worldwide, creating a serious public health problem and a high cost to the health systems. The etiology of CVD is multifactorial and it has several risk factors, such as dyslipidemia among others. Statins, inhibitors of cholesterol synthesis, are the most prescribed medications for dyslipidemia treatment. In different cellular models, statins modify the expression of genes involved in cholesterol homeostasis. However, there is less information about the post-transcriptional control exerted by the non-coding RNAs named microRNAs (MIRs) in the regulation of cholesterol, especially in response to statins. In order to investigate the impact of the lipid-lowering therapy on modulation of MIRs, the global expression profile of MIRs will be evaluated by PCR array technology in peripheral blood mononuclear cells (PBMC) from hypercholesterolemic (HC) individuals treated with atorvastatin and simvastatin. The expression of some mRNA regulated by MIRs will also be evaluated by real time PCR. The interaction of differentially expressed MIRs with the mRNA expression of target genes will be analyzed by bioinformatics tools (PicTar, miRBase, TargetScan, MicroCosm Target, miRDB e PITA). The network of interactions between genes regulated by MIRs will be studied using the Ingenuity Pathway Analysis software. Polymorphisms located in sequences of MIRs and target genes will be evaluated in a group of HC patients treated with atorvastatin to investigate the relationship with the pharmacological response. The results of this study will contribute to elucidate the mechanisms and molecular pathways involved in response to lipid-lowering medications. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ZAMBRANO, TOMAS; HIRATA, ROSARIO D. C.; HIRATA, MARIO H.; CERDA, ALVARO; SALAZAR, LUIS A. Statins differentially modulate microRNAs expression in peripheral cells of hyperlipidemic subjects: A pilot study. European Journal of Pharmaceutical Sciences, v. 117, p. 55-61, MAY 30 2018. Web of Science Citations: 3.

ZAMBRANO, TOMAS; HIRATA, ROSARIO D. C.; HIRATA, MARIO H.; CERDA, ALVARO; SALAZAR, LUIS A. Altered microRNome Profiling in Statin-Induced HepG2 Cells: A Pilot Study Identifying Potential new Biomarkers Involved in Lipid-Lowering Treatment. CARDIOVASCULAR DRUGS AND THERAPY, v. 29, n. 6, p. 509-518, DEC 2015. Web of Science Citations: 9.