Abstract
Bicuspid aortic valve (BAV), the most common congenital heart defect, is associated with an increased prevalence of aortic dilation, aortic rupture and aortic valve calcification. Endothelial cells (ECs) play a major role in vessel wall integrity. Little is known regarding EC function in BAV patients due to lack of patient derived primary ECs. Endothelial colony forming cells (ECFCs) have been reported to be a valid surrogate model for several cardiovascular pathologies, thereby facilitating an in vitro system to assess patient-specific endothelial dysfunction. Therefore, the aim of this study was to investigate cellular functions in ECFCs isolated from BAV patients. Outgrowth and proliferation of ECFCs from patients with BAV (n = 34) and controls with a tricuspid aortic valve (TAV, n = 10) were determined and related to patient characteristics. Interestingly, we were only able to generate ECFCs from TAV and BAV patients without aortic dilation, and failed to isolate ECFC colonies from patients with a dilated aorta. Analyzing EC function showed that while proliferation, cell size and endothelial-to-mesenchymal transition were similar in TAV and BAV ECFCs, migration and the wound healing capacity of BAV ECFCs is significantly higher compared to TAV ECFCs. Furthermore, calcification is blunted in BAV compared to TAV ECFCs. Our results reveal ECs dysfunction in BAV patients and future research is required to unravel the underlying mechanisms and to further validate ECFCs as a patient-specific in vitro model for BAV.
Highlights
Bicuspid aortic valve (BAV) is the most common congenital heart defect, present in 1–2% of the adult population worldwide
Our results demonstrate Endothelial colony forming cells (ECFCs) dysfunction in BAV patients compared to healthy TAV controls
We first investigated whether ECFCs can be isolated from BAV patients and TAV controls
Summary
Bicuspid aortic valve (BAV) is the most common congenital heart defect, present in 1–2% of the adult population worldwide. Patients with a BAV have an increased prevalence of dilation and even rupture of the ascending aorta, while aortic valve regurgitation or stenosis can occur [3]. Little is known about a possible role of the endothelium in aortic dilation in BAV patients. The endothelial cells (ECs) have become of increased interest in BAV pathology (reviewed in [6]). Altered EC migration, EC function and endothelial-to-mesenchymal transition (EndoMT) have been described in BAV patients [7,8]. Mutations in ROBO4 have recently been identified in BAV patients, which was shown to impair the barrier function of the ECs and induce EndoMT [9]
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