A Segmental Approach from Molecular Profiling to Medical Imaging to Study Bicuspid Aortic Valve Aortopathy
Bicuspid aortic valve (BAV) patients develop ascending aortic (AAo) dilation. The pathogenesis of BAV aortopathy (genetic vs. haemodynamic) remains unclear. This study aims to identify regional changes around the AAo wall in BAV patients with aortopathy, integrating molecular data and clinical imagi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/23/3721 |
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| author | Froso Sophocleous Estefania De Garate Maria Giulia Bigotti Maryam Anwar Eva Jover Aranzazu Chamorro-Jorganes Cha Rajakaruna Konstantina Mitrousi Viola De Francesco Aileen Wilson Serban Stoica Andrew Parry Umberto Benedetto Pierpaolo Chivasso Frances Gill Mark C. K. Hamilton Chiara Bucciarelli-Ducci Massimo Caputo Costanza Emanueli Giovanni Biglino |
| author_facet | Froso Sophocleous Estefania De Garate Maria Giulia Bigotti Maryam Anwar Eva Jover Aranzazu Chamorro-Jorganes Cha Rajakaruna Konstantina Mitrousi Viola De Francesco Aileen Wilson Serban Stoica Andrew Parry Umberto Benedetto Pierpaolo Chivasso Frances Gill Mark C. K. Hamilton Chiara Bucciarelli-Ducci Massimo Caputo Costanza Emanueli Giovanni Biglino |
| author_sort | Froso Sophocleous |
| collection | DOAJ |
| description | Bicuspid aortic valve (BAV) patients develop ascending aortic (AAo) dilation. The pathogenesis of BAV aortopathy (genetic vs. haemodynamic) remains unclear. This study aims to identify regional changes around the AAo wall in BAV patients with aortopathy, integrating molecular data and clinical imaging. BAV patients with aortopathy (n = 15) were prospectively recruited to surgically collect aortic tissue and measure molecular markers across the AAo circumference. Dilated (anterior/right) vs. non-dilated (posterior/left) circumferential segments were profiled for whole-genomic microRNAs (next-generation RNA sequencing, miRCURY LNA PCR), protein content (tandem mass spectrometry), and elastin fragmentation and degeneration (histomorphometric analysis). Integrated bioinformatic analyses of RNA sequencing and proteomic datasets identified five microRNAs (miR-128-3p, miR-210-3p, miR-150-5p, miR-199b-5p, and miR-21-5p) differentially expressed across the AAo circumference. Among them, three miRNAs (miR-128-3p, miR-150-5p, and miR-199b-5p) were predicted to have an effect on eight common target genes, whose expression was dysregulated, according to proteomic analyses, and involved in the vascular-endothelial growth-factor signalling, Hippo signalling, and arachidonic acid pathways. Decreased elastic fibre levels and elastic layer thickness were observed in the dilated segments. Additionally, in a subset of patients n = 6/15, a four-dimensional cardiac magnetic resonance (CMR) scan was performed. Interestingly, an increase in wall shear stress (WSS) was observed at the anterior/right wall segments, concomitantly with the differentially expressed miRNAs and decreased elastic fibres. This study identified new miRNAs involved in the BAV aortic wall and revealed the concomitant expressional dysregulation of miRNAs, proteins, and elastic fibres on the anterior/right wall in dilated BAV patients, corresponding to regions of elevated WSS. |
| first_indexed | 2024-03-09T17:51:06Z |
| format | Article |
| id | doaj.art-1e1ef6f261454ce09245229e4a94597d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:51:06Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-1e1ef6f261454ce09245229e4a94597d2023-11-24T10:42:41ZengMDPI AGCells2073-44092022-11-011123372110.3390/cells11233721A Segmental Approach from Molecular Profiling to Medical Imaging to Study Bicuspid Aortic Valve AortopathyFroso Sophocleous0Estefania De Garate1Maria Giulia Bigotti2Maryam Anwar3Eva Jover4Aranzazu Chamorro-Jorganes5Cha Rajakaruna6Konstantina Mitrousi7Viola De Francesco8Aileen Wilson9Serban Stoica10Andrew Parry11Umberto Benedetto12Pierpaolo Chivasso13Frances Gill14Mark C. K. Hamilton15Chiara Bucciarelli-Ducci16Massimo Caputo17Costanza Emanueli18Giovanni Biglino19Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol BS8 1TH, UKBristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol BS8 1TH, UKBristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol BS8 1TH, UKNational Heart and Lung Institute, Imperial College London, London SW7 2BX, UKBristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol BS8 1TH, UKNational Heart and Lung Institute, Imperial College London, London SW7 2BX, UKBristol Heart Institute, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol BS1 3NU, UKBristol Heart Institute, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol BS1 3NU, UKBristol Heart Institute, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol BS1 3NU, UKBristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol BS8 1TH, UKBristol Heart Institute, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol BS1 3NU, UKBristol Heart Institute, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol BS1 3NU, UKBristol Heart Institute, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol BS1 3NU, UKBristol Heart Institute, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol BS1 3NU, UKBristol Heart Institute, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol BS1 3NU, UKDepartment of Clinical Radiology, University Hospitals Bristol, Bristol Royal Infirmary, Bristol BS2 8EJ, UKBristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol BS8 1TH, UKBristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol BS8 1TH, UKNational Heart and Lung Institute, Imperial College London, London SW7 2BX, UKBristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol BS8 1TH, UKBicuspid aortic valve (BAV) patients develop ascending aortic (AAo) dilation. The pathogenesis of BAV aortopathy (genetic vs. haemodynamic) remains unclear. This study aims to identify regional changes around the AAo wall in BAV patients with aortopathy, integrating molecular data and clinical imaging. BAV patients with aortopathy (n = 15) were prospectively recruited to surgically collect aortic tissue and measure molecular markers across the AAo circumference. Dilated (anterior/right) vs. non-dilated (posterior/left) circumferential segments were profiled for whole-genomic microRNAs (next-generation RNA sequencing, miRCURY LNA PCR), protein content (tandem mass spectrometry), and elastin fragmentation and degeneration (histomorphometric analysis). Integrated bioinformatic analyses of RNA sequencing and proteomic datasets identified five microRNAs (miR-128-3p, miR-210-3p, miR-150-5p, miR-199b-5p, and miR-21-5p) differentially expressed across the AAo circumference. Among them, three miRNAs (miR-128-3p, miR-150-5p, and miR-199b-5p) were predicted to have an effect on eight common target genes, whose expression was dysregulated, according to proteomic analyses, and involved in the vascular-endothelial growth-factor signalling, Hippo signalling, and arachidonic acid pathways. Decreased elastic fibre levels and elastic layer thickness were observed in the dilated segments. Additionally, in a subset of patients n = 6/15, a four-dimensional cardiac magnetic resonance (CMR) scan was performed. Interestingly, an increase in wall shear stress (WSS) was observed at the anterior/right wall segments, concomitantly with the differentially expressed miRNAs and decreased elastic fibres. This study identified new miRNAs involved in the BAV aortic wall and revealed the concomitant expressional dysregulation of miRNAs, proteins, and elastic fibres on the anterior/right wall in dilated BAV patients, corresponding to regions of elevated WSS.https://www.mdpi.com/2073-4409/11/23/3721aortic segmentationmicroRNAsproteinswall shear stress |
| spellingShingle | Froso Sophocleous Estefania De Garate Maria Giulia Bigotti Maryam Anwar Eva Jover Aranzazu Chamorro-Jorganes Cha Rajakaruna Konstantina Mitrousi Viola De Francesco Aileen Wilson Serban Stoica Andrew Parry Umberto Benedetto Pierpaolo Chivasso Frances Gill Mark C. K. Hamilton Chiara Bucciarelli-Ducci Massimo Caputo Costanza Emanueli Giovanni Biglino A Segmental Approach from Molecular Profiling to Medical Imaging to Study Bicuspid Aortic Valve Aortopathy Cells aortic segmentation microRNAs proteins wall shear stress |
| title | A Segmental Approach from Molecular Profiling to Medical Imaging to Study Bicuspid Aortic Valve Aortopathy |
| title_full | A Segmental Approach from Molecular Profiling to Medical Imaging to Study Bicuspid Aortic Valve Aortopathy |
| title_fullStr | A Segmental Approach from Molecular Profiling to Medical Imaging to Study Bicuspid Aortic Valve Aortopathy |
| title_full_unstemmed | A Segmental Approach from Molecular Profiling to Medical Imaging to Study Bicuspid Aortic Valve Aortopathy |
| title_short | A Segmental Approach from Molecular Profiling to Medical Imaging to Study Bicuspid Aortic Valve Aortopathy |
| title_sort | segmental approach from molecular profiling to medical imaging to study bicuspid aortic valve aortopathy |
| topic | aortic segmentation microRNAs proteins wall shear stress |
| url | https://www.mdpi.com/2073-4409/11/23/3721 |
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