Endothelial Colony Forming Cells as an Autologous Model to Study Endothelial Dysfunction in Patients with a Bicuspid Aortic Valve.
Vera van de PolLidia R BonsKirsten LodderKonda Babu KurakulaGonzalo Sanchez-DuffhuesHans-Marc J SiebelinkJolien W Roos-HesselinkMarco C DeRuiterMarie-José T H GoumansPublished in: International journal of molecular sciences (2019)
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.
Keyphrases
- aortic valve
- aortic stenosis
- transcatheter aortic valve replacement
- aortic valve replacement
- ejection fraction
- transcatheter aortic valve implantation
- endothelial cells
- end stage renal disease
- chronic kidney disease
- oxidative stress
- induced apoptosis
- left ventricular
- cell proliferation
- stem cells
- cell therapy
- case report
- mesenchymal stem cells
- cell cycle arrest
- signaling pathway
- genome wide
- cell death
- coronary artery disease
- pulmonary arterial hypertension
- vascular endothelial growth factor
- pi k akt