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

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.

Non-Coding RNAs: New Dawn for Diabetes Mellitus Induced Erectile Dysfunction

“…Kazemi et al (2021) attempted to identify the conserved site for miRNAs, and revealed that the conserved miR-29-3p binding site is found in the 3'UTR of genes related with ED. (Tiraboschi et al, 2021).…”

“…Research by Gonçalves et al (2018) and Tiraboschi et al (2021) created three distinct types of ED models in rats: diabetic, alcoholic, or both. Their outcomes, however, are distinct.…”

“… Gonçalves et al (2018) discovered that in alcoholic and alcoholic–diabetic conditions, reduced expression of miR-199 and miR-155 boosted endothelin receptor (ETA and ERB) expression. Then, in another study, miR-15b, miR-16, miR-138, miR-221, and miR-222 could be considered prospective biomarkers for diabetic alcoholic ED ( Tiraboschi et al, 2021 ).…”

DNA methylation and regulation of gene expression: Guardian of our health

“…Significant changes in the ratio of vitamin intake were found to affect the CpG island methylation pattern in the loci of DNMT1, DNMT3A and DNMT3B, consequently leading to increased expression of the methyltransferases [ 29 ]. Even levels of miRNAs like that of miR-133 (linked to muscle and cardiac tissue metabolism and certain kinds of cancer) [ 54 , 58 , 65 , 85 , 86 , 98 , 101 ] and miR-221 (linked to oncogenesis) [ 10 , 25 , 50 , 56 , 60 , 71 , 79 , 90 , 96 , 100 ] changed in response to a skewed ratio of intake of the two vitamins. Other than sub or supra-optimal levels of folate or B12 intake, vitamin C or ascorbic acid consumption during the perinatal period also seems significant [ 19 ].…”

Oxidized soluble guanylyl cyclase causes erectile dysfunction in alcoholic mice

“…There is some experimental evidence in animal models to support a causal link between alcohol and ED (Aydinoglu et al, 2008; Leite et al, 2017; Lizarte et al, 2009; Tiraboschi et al, 2021; Yazir et al, 2012). Corpora cavernosa (CC) isolated from mice, rats or rabbits chronically exposed to alcohol show an impaired relaxation to acetylcholine or other muscarinic receptor agonists which stimulate the endothelium to release nitric oxide (NO) (Aydinoglu et al, 2008; Lizarte et al, 2009; Yazir et al, 2012).…”