Expression of MicroRNAs (miR-15b, miR-16, miR-138, miR-221, and miR-222) as Biomarkers of Endothelial Corpus Cavernosum Dysfunction in a Diabetic Alcoholic Murine Model

Ricardo Brianezi Tiraboschi, MD, PhD; Fermino Sanches Lizarte Neto, PhD; Daniela Pretti da Cunha Tirapelli, PhD; Jose de Bessa, Jr, MD, PhD; Eduardo Paula Miranda, MD, PhD; Mucio Luiz de Assis Cirino, PhD; Luis Fernando Tirapelli, PhD; Silvio Tucci, Jr, MD, PhD; Carlos Augusto Fernandes Molina, MD, PhD

Sexual Medicine (Apr 2021)

Expression of MicroRNAs (miR-15b, miR-16, miR-138, miR-221, and miR-222) as Biomarkers of Endothelial Corpus Cavernosum Dysfunction in a Diabetic Alcoholic Murine Model

Ricardo Brianezi Tiraboschi, MD, PhD,
Fermino Sanches Lizarte Neto, PhD,
Daniela Pretti da Cunha Tirapelli, PhD,
Jose de Bessa, Jr, MD, PhD,
Eduardo Paula Miranda, MD, PhD,
Mucio Luiz de Assis Cirino, PhD,
Luis Fernando Tirapelli, PhD,
Silvio Tucci, Jr, MD, PhD,
Carlos Augusto Fernandes Molina, MD, PhD

Affiliations

Ricardo Brianezi Tiraboschi, MD, PhD: Department of Surgery, Division of Urology, Universidade Estadual de Feira de Santana, Medical School, State University of Feira de Santana, Feira de Santana, Brazil; Division of Urology, University of São Paulo, Ribeirão Preto Medical School, Surgery and Anatomy, Ribeirao Preto, São Paulo, Brazil
Fermino Sanches Lizarte Neto, PhD: University of São Paulo, Ribeirão Preto Medical School, Surgery and Anatomy, Ribeirao Preto, São Paulo, Brazil
Daniela Pretti da Cunha Tirapelli, PhD: University of São Paulo, Ribeirão Preto Medical School, Surgery and Anatomy, Ribeirao Preto, São Paulo, Brazil
Jose de Bessa, Jr, MD, PhD: Department of Surgery, Division of Urology, Universidade Estadual de Feira de Santana, Medical School, State University of Feira de Santana, Feira de Santana, Brazil; Corresponding Author: Jose de Bessa Jr, MD, PhD, Department of Surgery, Division of Urology, Universidade Estadual de Feira de Santana, Medical School, State University of Feira de Santana, Av. Transnordestina, s/n - Novo Horizonte, Feira de Santana, BA, BR 44036-900, Brazil. Tel: +557536257880
Eduardo Paula Miranda, MD, PhD: Division of Urology, Universidade Federal do Ceara, Fortaleza, Brazil
Mucio Luiz de Assis Cirino, PhD: University of São Paulo, Ribeirão Preto Medical School, Surgery and Anatomy, Ribeirao Preto, São Paulo, Brazil
Luis Fernando Tirapelli, PhD: University of São Paulo, Ribeirão Preto Medical School, Surgery and Anatomy, Ribeirao Preto, São Paulo, Brazil
Silvio Tucci, Jr, MD, PhD: Division of Urology, University of São Paulo, Ribeirão Preto Medical School, Surgery and Anatomy, Ribeirao Preto, São Paulo, Brazil
Carlos Augusto Fernandes Molina, MD, PhD: Division of Urology, University of São Paulo, Ribeirão Preto Medical School, Surgery and Anatomy, Ribeirao Preto, São Paulo, Brazil

Journal volume & issue: Vol. 9, no. 2
p. 100326

Abstract

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ABSTRACT: Introduction: MicroRNAs (miRNAs) are short noncoding RNA molecules that regulate gene expression and are related to endothelial dysfunction (EnD). Recently, miRNAs have also been explored as potential biomarkers and target molecular therapy of erectile dysfunction (ED). Could the miRNAs be the tip of the iceberg of chronic arterial disease foreshadowed by the ED? Aim: To investigate the expression of miR-15b, miR-16, miR-138, miR-221, and miR-222 in corpus cavernosum (CC) and peripheral blood in a rat model of endothelium dysfunction secondary to diabetes (DM) and alcohol consumption to assess potential endothelial lesion biomarkers. Methods: Twenty males Wistar rats were divided into 4 groups: control group (C), alcohol consumption group (A), diabetic group (D), diabetic-alcohol consumption group (D + A). DM was alloxan-induced and alcohol consumption was through progressive increase of ethanol concentration in drinkable water. After 7 weeks, miRNAs expressions from CC and blood sample were evaluated by real-time PCR. Functional assessment of CC was performed in an acetylcholine endothelium-dependent relaxation pharmacological study. Main Outcome Measure: miRNA expression in CC and blood were evaluated; pharmacological study in CC strips was conducted to validate EnD. Results: We found that 3 miRNAs (miR-16, miR-221, and miR-222) were downregulated in the CC in the D+A group, while all 5 miRNAs were downregulated in the blood of D and D + A groups. The endothelium-dependent relaxation induced by acetylcholine was significantly decreased in groups A, D, and D + A. Diagnostic accuracy estimated by AUC, to discriminating groups A, D, and D + A from controls, was superior to >0.9 in all plasmatic miRNAs. Conclusion: miRNAs downregulation was identified in both CC and blood notably in DM associated with alcohol consumption animals (D + A), the greatest endothelial injury potential group. Serum miRNAs have also demonstrated high diagnostic accuracy properties in predicting CC relaxation dysfunction labeling EnD. RB Tiraboschi, FSL Neto, DP da Cunha Tirapelli, et al. Expression of MicroRNAs (miR-15b, miR-16, miR-138, miR-221, and miR-222) as Biomarkers of Endothelial Corpus Cavernosum Dysfunction in a Diabetic Alcoholic Murine Model. Sex Med 2021;9:100326.

Published in Sexual Medicine

ISSN: 2050-1161 (Online)
Publisher: Oxford University Press
Country of publisher: United Kingdom
LCC subjects: Medicine
Website: https://academic.oup.com/smoa

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