The main objective of this study is to find biomarkers for the prognosis of the BAV patients by investigating ECFC and EPC functioning, and to gain knowledge on physiological and pathological processes in patients by investigating molecular…
ID
Source
Brief title
Condition
- Cardiac valve disorders
- Cardiac and vascular disorders congenital
- Aneurysms and artery dissections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The parameters studied are endothelial cell communication and endothelial cell
function. -
- The cell communication will be primarily studied in the ECFCs. The response
of smooth muscle cells to the presence of ECFC secreted factors will determine
what the focus will be of the study. There are 4 likely candidates:
inflammatory factors, growth factors, nitric oxide regulation and extracellular
matrix remodelling.
- Endothelial cell function will be studied in the EMT response, migration and
calcification.
- The results from the ECFCs will then be studied in the EPC*s to look for
potential biomarkers
Secondary outcome
The results obtained with the ECFC*s will studied for potential links to
valvular development. This might elucidate the pathogenesis of bicuspid aortic
valves.
Background summary
Rationale: Bicuspid aortic valve (BAV), a heart valve with only two leaflets
instead of three, is the most common congenital heart malformation. In a
significant proportion of patients stenosis or insufficiency of the aortic
valves and/or ascending aortic aneurysm contribute to important morbidity and
mortality. Turner patients are more prone to the development of cardiovascular
diseases, amongst which BAV and dilation. Endothelial dysfunction has been
reported in BAV patients, possibly indicating a role for the endothelium in the
development of stenosis, regurgitation and/or development of aortic aneurysms.
To investigate the endothelial cell functioning and potential biomarkers,
endothelial progenitor cells (EPCs) and endothelial colony forming cells
(ECFCs) can be isolated from peripheral blood and can be cultured for in vitro
experiments. Cell function can be investigated by measuring parameters as
migration and response to different signals.
This study is an in vitro cell functioning study to unravel biomarkers of
adverse outcome and to explore the pathogenic basis of bicuspid aortic valves
and its associated pathologies. This will help to individualize treatment
protocols and develop novel therapeutic strategies.
Hypothesis: (1) Cell function will correlate with aortic valve
stenosis/regurgitation and aortic root diameter in patients with BAV disease.
(2) Cell functional profiles will differ between patients with stenosis or
regurgitation of the valves and aortic root dilation and may identify high-risk
patients and low risk patients.
Study objective
The main objective of this study is to find biomarkers for the prognosis of the
BAV patients by investigating ECFC and EPC functioning, and to gain knowledge
on physiological and pathological processes in patients by investigating
molecular signalling in these cells.
Objectives:
• To describe the functional characteristics of ECFCs and EPCs of BAV patients;
• To identify cell characteristics associated with the valve
stenosis/regurgitation and/or root dilation;
• To associate patient follow-up data to cell characteristics to define
potential biomarkers;
• To identify differences in cell functioning of BAV patients with and without
Turner Syndrome;
• To identify molecular signalling pathways that are disturbed in
stenosis/regurgitation and/or root dilation.
Study design
In vitro study.
Duration: 3 years inclusion, 15 years follow-up
Setting: Outpatient clinic of an academic hospital.
Study burden and risks
The burden to the patient is one time venous blood sampling. Venous blood
sampling of 80 ml has a very low risk. The time consumption for the patient is
estimated to be less than 15 minutes.
Einthovenweg 20
Leiden 2333 ZA
NL
Einthovenweg 20
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
• aged >= 18 years;
• capable of understanding and signing informed consent.
• echocardiogram at most 1 year and 2 months before blood drawing
• for the patient population: Bicuspid aortic valves
Exclusion criteria
• Consuming more than 3 units of alcohol the evening before drawing blood
For the control population:
• Valvular stenosis
• Regurgitation
• Aortic dilation
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL55229.058.15 |