Experimental evidence of the genetic hypothesis on the etiology of bicuspid aortic valve aortopathy in the hamster model
Bicuspid aortopathy occurs in approximately 50% of patients with bicuspid aortic valve (BAV), the most prevalent congenital cardiac malformation. Although different molecular players and etiological factors (genetic and hemodynamic) have been suggested to be involved in aortopathy predisposition and...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.928362/full |
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| author | María Teresa Soto-Navarrete María Teresa Soto-Navarrete Bárbara Pozo-Vilumbrales Bárbara Pozo-Vilumbrales Miguel Ángel López-Unzu Miguel Ángel López-Unzu Miguel Ángel López-Unzu Carmen Rueda-Martínez M. Carmen Fernández M. Carmen Fernández M. Carmen Fernández Ana Carmen Durán Ana Carmen Durán Francisco Javier Pavón-Morón Francisco Javier Pavón-Morón Francisco Javier Pavón-Morón Jorge Rodríguez-Capitán Jorge Rodríguez-Capitán Jorge Rodríguez-Capitán Borja Fernández Borja Fernández Borja Fernández |
| author_facet | María Teresa Soto-Navarrete María Teresa Soto-Navarrete Bárbara Pozo-Vilumbrales Bárbara Pozo-Vilumbrales Miguel Ángel López-Unzu Miguel Ángel López-Unzu Miguel Ángel López-Unzu Carmen Rueda-Martínez M. Carmen Fernández M. Carmen Fernández M. Carmen Fernández Ana Carmen Durán Ana Carmen Durán Francisco Javier Pavón-Morón Francisco Javier Pavón-Morón Francisco Javier Pavón-Morón Jorge Rodríguez-Capitán Jorge Rodríguez-Capitán Jorge Rodríguez-Capitán Borja Fernández Borja Fernández Borja Fernández |
| author_sort | María Teresa Soto-Navarrete |
| collection | DOAJ |
| description | Bicuspid aortopathy occurs in approximately 50% of patients with bicuspid aortic valve (BAV), the most prevalent congenital cardiac malformation. Although different molecular players and etiological factors (genetic and hemodynamic) have been suggested to be involved in aortopathy predisposition and progression, clear etiophysiopathological mechanisms of disease are still missing. The isogenic (genetically uniform) hamster (T) strain shows 40% incidence of BAV, but aortic dilatations have not been detected in this model. We have performed comparative anatomical, histological and molecular analyses of the ascending aorta of animals with tricuspid aortic valve (TAV) and BAV from the T strain (TTAV and TBAV, respectively) and with TAV from a control strain (HTAV). Aortic diameter, smooth muscle apoptosis, elastic waviness, and Tgf-β and Fbn-2 expression were significantly increased in T strain animals, regardless of the valve morphology. Strain and aortic valve morphology did not affect Mmp-9 expression, whereas Mmp-2 transcripts were reduced in BAV animals. eNOS protein amount decreased in both TBAV and TTAV compared to HTAV animals. Thus, histomorphological and molecular alterations of the ascending aorta appear in a genetically uniform spontaneous hamster model irrespective of the aortic valve morphology. This is a direct experimental evidence supporting the genetic association between BAV and aortic dilatation. This model may represent a population of patients with predisposition to BAV aortopathy, in which increased expression of Tgf-β and Fbn-2 alters elastic lamellae structure and induces cell apoptosis mediated by eNOS. Patients either with TAV or BAV with the same genetic defect may show the same risk to develop bicuspid aortopathy. |
| first_indexed | 2024-04-13T11:15:53Z |
| format | Article |
| id | doaj.art-b2c6667fd3264855b68c6cbba40fcec4 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-13T11:15:53Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-b2c6667fd3264855b68c6cbba40fcec42022-12-22T02:48:59ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-08-01910.3389/fcvm.2022.928362928362Experimental evidence of the genetic hypothesis on the etiology of bicuspid aortic valve aortopathy in the hamster modelMaría Teresa Soto-Navarrete0María Teresa Soto-Navarrete1Bárbara Pozo-Vilumbrales2Bárbara Pozo-Vilumbrales3Miguel Ángel López-Unzu4Miguel Ángel López-Unzu5Miguel Ángel López-Unzu6Carmen Rueda-Martínez7M. Carmen Fernández8M. Carmen Fernández9M. Carmen Fernández10Ana Carmen Durán11Ana Carmen Durán12Francisco Javier Pavón-Morón13Francisco Javier Pavón-Morón14Francisco Javier Pavón-Morón15Jorge Rodríguez-Capitán16Jorge Rodríguez-Capitán17Jorge Rodríguez-Capitán18Borja Fernández19Borja Fernández20Borja Fernández21Departamento de Biología Animal, Facultad de Ciencias, Universidad de Málaga, Málaga, SpainInstituto de Investigaciones Biomédicas de Málaga y Plataforma en Nanomedicina, Universidad de Málaga, Málaga, SpainDepartamento de Biología Animal, Facultad de Ciencias, Universidad de Málaga, Málaga, SpainInstituto de Investigaciones Biomédicas de Málaga y Plataforma en Nanomedicina, Universidad de Málaga, Málaga, SpainDepartamento de Biología Animal, Facultad de Ciencias, Universidad de Málaga, Málaga, SpainInstituto de Investigaciones Biomédicas de Málaga y Plataforma en Nanomedicina, Universidad de Málaga, Málaga, SpainSpanish National Centre for Cardiovascular Research, Madrid, SpainDepartamento de Biología Animal, Facultad de Ciencias, Universidad de Málaga, Málaga, SpainDepartamento de Biología Animal, Facultad de Ciencias, Universidad de Málaga, Málaga, SpainInstituto de Investigaciones Biomédicas de Málaga y Plataforma en Nanomedicina, Universidad de Málaga, Málaga, SpainDepartamento de Anatomía Humana, Medicina Legal e Historia de la Medicina, Facultad de Medicina, Universidad de Málaga, Málaga, SpainDepartamento de Biología Animal, Facultad de Ciencias, Universidad de Málaga, Málaga, SpainInstituto de Investigaciones Biomédicas de Málaga y Plataforma en Nanomedicina, Universidad de Málaga, Málaga, SpainInstituto de Investigaciones Biomédicas de Málaga y Plataforma en Nanomedicina, Universidad de Málaga, Málaga, SpainCentro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Málaga, SpainUnidad de Gestión Clínica del Corazón, Hospital Universitario Virgen de la Victoria, Málaga, SpainInstituto de Investigaciones Biomédicas de Málaga y Plataforma en Nanomedicina, Universidad de Málaga, Málaga, SpainCentro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Málaga, SpainUnidad de Gestión Clínica del Corazón, Hospital Universitario Virgen de la Victoria, Málaga, SpainDepartamento de Biología Animal, Facultad de Ciencias, Universidad de Málaga, Málaga, SpainInstituto de Investigaciones Biomédicas de Málaga y Plataforma en Nanomedicina, Universidad de Málaga, Málaga, SpainCentro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Málaga, SpainBicuspid aortopathy occurs in approximately 50% of patients with bicuspid aortic valve (BAV), the most prevalent congenital cardiac malformation. Although different molecular players and etiological factors (genetic and hemodynamic) have been suggested to be involved in aortopathy predisposition and progression, clear etiophysiopathological mechanisms of disease are still missing. The isogenic (genetically uniform) hamster (T) strain shows 40% incidence of BAV, but aortic dilatations have not been detected in this model. We have performed comparative anatomical, histological and molecular analyses of the ascending aorta of animals with tricuspid aortic valve (TAV) and BAV from the T strain (TTAV and TBAV, respectively) and with TAV from a control strain (HTAV). Aortic diameter, smooth muscle apoptosis, elastic waviness, and Tgf-β and Fbn-2 expression were significantly increased in T strain animals, regardless of the valve morphology. Strain and aortic valve morphology did not affect Mmp-9 expression, whereas Mmp-2 transcripts were reduced in BAV animals. eNOS protein amount decreased in both TBAV and TTAV compared to HTAV animals. Thus, histomorphological and molecular alterations of the ascending aorta appear in a genetically uniform spontaneous hamster model irrespective of the aortic valve morphology. This is a direct experimental evidence supporting the genetic association between BAV and aortic dilatation. This model may represent a population of patients with predisposition to BAV aortopathy, in which increased expression of Tgf-β and Fbn-2 alters elastic lamellae structure and induces cell apoptosis mediated by eNOS. Patients either with TAV or BAV with the same genetic defect may show the same risk to develop bicuspid aortopathy.https://www.frontiersin.org/articles/10.3389/fcvm.2022.928362/fullbicuspid aortic valve (BAV)aortic dilatationpathophysiologyetiologyanimal modelhamster |
| spellingShingle | María Teresa Soto-Navarrete María Teresa Soto-Navarrete Bárbara Pozo-Vilumbrales Bárbara Pozo-Vilumbrales Miguel Ángel López-Unzu Miguel Ángel López-Unzu Miguel Ángel López-Unzu Carmen Rueda-Martínez M. Carmen Fernández M. Carmen Fernández M. Carmen Fernández Ana Carmen Durán Ana Carmen Durán Francisco Javier Pavón-Morón Francisco Javier Pavón-Morón Francisco Javier Pavón-Morón Jorge Rodríguez-Capitán Jorge Rodríguez-Capitán Jorge Rodríguez-Capitán Borja Fernández Borja Fernández Borja Fernández Experimental evidence of the genetic hypothesis on the etiology of bicuspid aortic valve aortopathy in the hamster model Frontiers in Cardiovascular Medicine bicuspid aortic valve (BAV) aortic dilatation pathophysiology etiology animal model hamster |
| title | Experimental evidence of the genetic hypothesis on the etiology of bicuspid aortic valve aortopathy in the hamster model |
| title_full | Experimental evidence of the genetic hypothesis on the etiology of bicuspid aortic valve aortopathy in the hamster model |
| title_fullStr | Experimental evidence of the genetic hypothesis on the etiology of bicuspid aortic valve aortopathy in the hamster model |
| title_full_unstemmed | Experimental evidence of the genetic hypothesis on the etiology of bicuspid aortic valve aortopathy in the hamster model |
| title_short | Experimental evidence of the genetic hypothesis on the etiology of bicuspid aortic valve aortopathy in the hamster model |
| title_sort | experimental evidence of the genetic hypothesis on the etiology of bicuspid aortic valve aortopathy in the hamster model |
| topic | bicuspid aortic valve (BAV) aortic dilatation pathophysiology etiology animal model hamster |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.928362/full |
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