On the prospect of serum exosomal miRNA profiling and protein biomarkers for the diagnosis of ascending aortic dilatation in patients with bicuspid and tricuspid aortic valve

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: To determine the impact of circulating miRNA and protein activity on the severity of ascending aortic dilatation in patients with bicuspid (BAV) and tricuspid aortic valve (TAV). Methods: By reverse transcription polymerase chain reaction, exosomal circulating expression levels (versus healthy aorta) of miRNAs and absolute levels of transforming growth factor β (TGF-β), matrix metalloproteinases (MMP-2, -3 and -9), tissue inhibitors (TIMP-1, -2, -3 and -4), and soluble receptors for advanced glycation end products AGEs (sRAGE) were evaluated in ascending dilated aortas of 71 patients with different valve morphotype. Results: Less-dilated ascending aorta exhibited a specific miRNA signature (i.e., miR-126 miR-15b, miR-195, miR-221, miR24, miR-30b and miR-320a), which was statistically different from that of severely-dilated ascending aorta. Among these analytes, miR-15b was the most significant (p < 0.001) and resulted as an independent predictor of aortic dilatation (β = −1.099, p = 0.041). When patients were grouped according to aortic valve morphology, miRNAs and protein proteolytic activity were different between BAV and TAV in the expression level of miR-133a, miR-155, miR-320a, miR-34a(#000425), miR-34a(#000426), miR-494 and measurements of TGF-β and MMP-3, MMP-9, TIMP-4. The circulating level of miR-34a(#000426) was negatively correlated to the aortic wall elasticity of bicuspid patients (R = −0.653 and p = 0.011), suggesting an apparent different mechanism of aortic wall degeneration specific for BAV. Conclusions: Taken these biomarkers together, we demonstrated that the severity of aortic size and valve morphology differently modulates miRNA analytes and protein proteolytic activity in patients with ascending aortic dilatation, and this may be useful to design new therapies that inhibit miRNAs.

Original languageEnglish
Pages (from-to)230-236
Number of pages7
JournalInternational Journal of Cardiology
Volume273
DOIs
Publication statusPublished - Dec 15 2018

Fingerprint

Tricuspid Valve
MicroRNAs
Dilatation
Biomarkers
Aortic Valve
Aorta
Serum
Matrix Metalloproteinases
Proteins
Bicuspid
Transforming Growth Factors
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase 2
Elasticity
Reverse Transcription
Bicuspid Aortic Valve
Polymerase Chain Reaction

Keywords

  • Ascending aortic dilatation
  • Bicuspid aortic valve
  • Matrix metalloproteinases
  • MicroRNA
  • Tissue inhibitors
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{81f36a8258414486b7c983c563fc4886,
title = "On the prospect of serum exosomal miRNA profiling and protein biomarkers for the diagnosis of ascending aortic dilatation in patients with bicuspid and tricuspid aortic valve",
abstract = "Background: To determine the impact of circulating miRNA and protein activity on the severity of ascending aortic dilatation in patients with bicuspid (BAV) and tricuspid aortic valve (TAV). Methods: By reverse transcription polymerase chain reaction, exosomal circulating expression levels (versus healthy aorta) of miRNAs and absolute levels of transforming growth factor β (TGF-β), matrix metalloproteinases (MMP-2, -3 and -9), tissue inhibitors (TIMP-1, -2, -3 and -4), and soluble receptors for advanced glycation end products AGEs (sRAGE) were evaluated in ascending dilated aortas of 71 patients with different valve morphotype. Results: Less-dilated ascending aorta exhibited a specific miRNA signature (i.e., miR-126 miR-15b, miR-195, miR-221, miR24, miR-30b and miR-320a), which was statistically different from that of severely-dilated ascending aorta. Among these analytes, miR-15b was the most significant (p < 0.001) and resulted as an independent predictor of aortic dilatation (β = −1.099, p = 0.041). When patients were grouped according to aortic valve morphology, miRNAs and protein proteolytic activity were different between BAV and TAV in the expression level of miR-133a, miR-155, miR-320a, miR-34a(#000425), miR-34a(#000426), miR-494 and measurements of TGF-β and MMP-3, MMP-9, TIMP-4. The circulating level of miR-34a(#000426) was negatively correlated to the aortic wall elasticity of bicuspid patients (R = −0.653 and p = 0.011), suggesting an apparent different mechanism of aortic wall degeneration specific for BAV. Conclusions: Taken these biomarkers together, we demonstrated that the severity of aortic size and valve morphology differently modulates miRNA analytes and protein proteolytic activity in patients with ascending aortic dilatation, and this may be useful to design new therapies that inhibit miRNAs.",
keywords = "Ascending aortic dilatation, Bicuspid aortic valve, Matrix metalloproteinases, MicroRNA, Tissue inhibitors, Transforming growth factor-β",
author = "Alessia Gallo and Valentina Agnese and Claudia Coronnello and Raffa, {Giuseppe M.} and Diego Bellavia and Conaldi, {Pier Giulio} and Michele Pilato and Salvatore Pasta",
year = "2018",
month = "12",
day = "15",
doi = "10.1016/j.ijcard.2018.10.005",
language = "English",
volume = "273",
pages = "230--236",
journal = "International Journal of Cardiology",
issn = "0167-5273",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - On the prospect of serum exosomal miRNA profiling and protein biomarkers for the diagnosis of ascending aortic dilatation in patients with bicuspid and tricuspid aortic valve

AU - Gallo, Alessia

AU - Agnese, Valentina

AU - Coronnello, Claudia

AU - Raffa, Giuseppe M.

AU - Bellavia, Diego

AU - Conaldi, Pier Giulio

AU - Pilato, Michele

AU - Pasta, Salvatore

PY - 2018/12/15

Y1 - 2018/12/15

N2 - Background: To determine the impact of circulating miRNA and protein activity on the severity of ascending aortic dilatation in patients with bicuspid (BAV) and tricuspid aortic valve (TAV). Methods: By reverse transcription polymerase chain reaction, exosomal circulating expression levels (versus healthy aorta) of miRNAs and absolute levels of transforming growth factor β (TGF-β), matrix metalloproteinases (MMP-2, -3 and -9), tissue inhibitors (TIMP-1, -2, -3 and -4), and soluble receptors for advanced glycation end products AGEs (sRAGE) were evaluated in ascending dilated aortas of 71 patients with different valve morphotype. Results: Less-dilated ascending aorta exhibited a specific miRNA signature (i.e., miR-126 miR-15b, miR-195, miR-221, miR24, miR-30b and miR-320a), which was statistically different from that of severely-dilated ascending aorta. Among these analytes, miR-15b was the most significant (p < 0.001) and resulted as an independent predictor of aortic dilatation (β = −1.099, p = 0.041). When patients were grouped according to aortic valve morphology, miRNAs and protein proteolytic activity were different between BAV and TAV in the expression level of miR-133a, miR-155, miR-320a, miR-34a(#000425), miR-34a(#000426), miR-494 and measurements of TGF-β and MMP-3, MMP-9, TIMP-4. The circulating level of miR-34a(#000426) was negatively correlated to the aortic wall elasticity of bicuspid patients (R = −0.653 and p = 0.011), suggesting an apparent different mechanism of aortic wall degeneration specific for BAV. Conclusions: Taken these biomarkers together, we demonstrated that the severity of aortic size and valve morphology differently modulates miRNA analytes and protein proteolytic activity in patients with ascending aortic dilatation, and this may be useful to design new therapies that inhibit miRNAs.

AB - Background: To determine the impact of circulating miRNA and protein activity on the severity of ascending aortic dilatation in patients with bicuspid (BAV) and tricuspid aortic valve (TAV). Methods: By reverse transcription polymerase chain reaction, exosomal circulating expression levels (versus healthy aorta) of miRNAs and absolute levels of transforming growth factor β (TGF-β), matrix metalloproteinases (MMP-2, -3 and -9), tissue inhibitors (TIMP-1, -2, -3 and -4), and soluble receptors for advanced glycation end products AGEs (sRAGE) were evaluated in ascending dilated aortas of 71 patients with different valve morphotype. Results: Less-dilated ascending aorta exhibited a specific miRNA signature (i.e., miR-126 miR-15b, miR-195, miR-221, miR24, miR-30b and miR-320a), which was statistically different from that of severely-dilated ascending aorta. Among these analytes, miR-15b was the most significant (p < 0.001) and resulted as an independent predictor of aortic dilatation (β = −1.099, p = 0.041). When patients were grouped according to aortic valve morphology, miRNAs and protein proteolytic activity were different between BAV and TAV in the expression level of miR-133a, miR-155, miR-320a, miR-34a(#000425), miR-34a(#000426), miR-494 and measurements of TGF-β and MMP-3, MMP-9, TIMP-4. The circulating level of miR-34a(#000426) was negatively correlated to the aortic wall elasticity of bicuspid patients (R = −0.653 and p = 0.011), suggesting an apparent different mechanism of aortic wall degeneration specific for BAV. Conclusions: Taken these biomarkers together, we demonstrated that the severity of aortic size and valve morphology differently modulates miRNA analytes and protein proteolytic activity in patients with ascending aortic dilatation, and this may be useful to design new therapies that inhibit miRNAs.

KW - Ascending aortic dilatation

KW - Bicuspid aortic valve

KW - Matrix metalloproteinases

KW - MicroRNA

KW - Tissue inhibitors

KW - Transforming growth factor-β

UR - http://www.scopus.com/inward/record.url?scp=85054392361&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054392361&partnerID=8YFLogxK

U2 - 10.1016/j.ijcard.2018.10.005

DO - 10.1016/j.ijcard.2018.10.005

M3 - Article

C2 - 30297190

AN - SCOPUS:85054392361

VL - 273

SP - 230

EP - 236

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

ER -