Related Experiment Video
Updated: Apr 16, 2026

A Rabbit Aortic Valve Stenosis Model Induced by Direct Balloon Injury
Published on: March 31, 2023
Aneurysm development in patients with a bicuspid aortic valve is not associated with transforming growth factor-β
Valentina Paloschi1, Jesper R Gådin2, Shaukat Khan2
1From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine (V.P., J.R.G., H.M.B., L.D., S.M., P.E.), Vascular Surgery Section, Department of Molecular Medicine and Surgery (J.R.), and Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Center for Cardiac Research, Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE (S.K., T.T.); Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands (J.H.M.L.); and Department of Cardiac Surgery, University Clinic of Schleswig-Holstein Campus Luebeck, Luebeck, Germany (S.A.M.). Valentina.Paloschi@ki.se.
Objective:
Patients with bicuspid aortic valve (BAV) have an increased risk of developing ascending aortic aneurysms. Transforming growth factor-β (TGFβ) is a crucial factor of vascular remodeling, the impaired signaling of which can alter the structure and composition of the extracellular matrix. In this study, we analyzed the activity of TGFβ in aneurysmal and nonaneurysmal ascending aorta from BAV patients, using tricuspid aortic valve (TAV) patients as a reference group.
Approach And Results:
The response to exogenous TGFβ was analyzed with regard to gene expression in primary aortic smooth muscle cells that were isolated from 7 BAV and 5 TAV patients and in valve fibroblasts from 7 BAV and 8 TAV patients. The set of genes that were significantly changed by TGFβ (217 genes) was compared with gene expression profiles of the ascending aorta from BAV and TAV patients (139 arrays). By principle component analysis, based on the 217 genes, gene expression differed significantly in the intima/media region between aneurysmal BAV and TAV aortas, driven by the response in TAV patients. During aneurysm development the levels of phosphorylated SMADs and the availability of free TGFβ were lower in BAV patients compared with TAV. Confocal microscopy analysis showed a higher colocalization of latency associated peptide and latent TGFβ binding protein 3 in BAV aortas.
Conclusions:
Our findings suggest that TGFβ activation during aneurysm formation is muted in patients with BAV, possibly as a result of an increased TGFβ sequestration in the extracellular space.
More Related Videos
04:30Investigating Aortic Valve Calcification via Isolation and Culture of T Lymphocytes using Feeder Cells from Irradiated Buffy Coat
Published on: February 4, 2021
05:47Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro
Published on: May 10, 2021
Related Concept Videos
Aortic Regurgitation I: Introduction
Aortic Regurgitation II: Clinical Features and Diagnostic Tests
Aneurysm I: Introduction
Aneurysm II: Clinical Manifestations and Diagnostic Studies
Aortic Regurgitation III: Medical Management
Mitral Valve Prolapse I: Introduction