RT Journal Article
T1 Experimental evidence of the genetic hypothesis on the etiology of bicuspid aortic valve aortopathy in the hamster model.
A1 Soto-Navarrete, María Teresa
A1 Pozo-Vilumbrales, Bárbara
A1 López-Unzu, Miguel Ángel
A1 Rueda-Martínez, Carmen
A1 Fernández, M Carmen
A1 Durán, Ana Carmen
A1 Pavón-Morón, Francisco Javier
A1 Rodríguez-Capitán, Jorge
A1 Fernández, Borja
K1 animal model
K1 aortic dilatation
K1 bicuspid aortic valve (BAV)
K1 etiology
K1 hamster
K1 pathophysiology
AB 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.
SN 2297-055X
YR 2022
FD 2022-08-08
LK http://hdl.handle.net/10668/20553
UL http://hdl.handle.net/10668/20553
LA en
DS RISalud
RD Apr 7, 2025