Experimental aortic valve stenosis leads to aortopathy with impaired aortic function and tissue redox dysbalance

Christine Quast (Düsseldorf)1, M. Nankinova (Düsseldorf)1, I. Gyamfi-Poku (Düsseldorf)1, R. Chennupati (Düsseldorf)1, T. Zeus (Düsseldorf)1, U. Flögel (Düsseldorf)2, M. Kelm (Düsseldorf)1

1Universitätsklinikum Düsseldorf Klinik für Kardiologie, Pneumologie und Angiologie Düsseldorf, Deutschland; 2Universitätsklinikum Düsseldorf Institut für Molekulare Kardiologie Düsseldorf, Deutschland


Background: While aortopathy is a known entity in biscuspid aortic valve disease, aortopathy in tricuspid aortic valve stenosis and its underlying molecular pathophysiology with potential impact on functional impairment are largely unknown. The aim of this study is to clarify alterations in aortic function and tissue characteristics of aortopathy in tricuspid valve stenosis irrespective of genetic variants in aortic valve stenosis.

Methods: We investigated aortic function and moelcular charasteristics in aortic valve stenosis (AS) after induction of aortic valve stenosis in a well-standardised model. C57/Bl6 mice were subjected to a wire injury to induce AS. Four weeks after induction, AS was verified by echocardiography. Aortic rings and femoral arteries were analysed in organ bath and wire myograph. Expression levels on mRNA and protein levels were analysed in aortic tissue. Nitrite/RXNO and nitrate levels were determined in aortic tissue bei CLD and HPLC. Redox status (GSH/GSSG ratio) and expression of genes involved in oxidative stress in the aortic tissue were analysed.

Results: In the murine model, AS was associated with significantly impaired aortic function in organ bath experiments while vascular function of femoral arteries was preserved. Nitrite and nitrate levels did not differ between groups. Aortic dysfunction was associated with significantly increased total eNOS protein levels and redox dysbalance in aortic tissue.

Conclusions: Our results hint at an aortopathy in experimental AS characterised by redox dysbalance and functional impairment with potential compensatory upregulation of eNOS protein levels and catalse gene expression.

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