Male-female Differences in Immunohistological and Biomechanical Properties of the Thoracic Aorta

Study Overview
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Brief Summary
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Thoracic aortic aneurysms (TAA) result from progressive dilatation of the thoracic aorta and confer a risk for aortic dissection or rupture, which is associated with significant morbidity and mortality. In the Netherlands there are an estimated 200.000 adults with TAA, and annually 600 deaths after aortic dissection or rupture. There are clear differences in the incidence of TAA between men and women, with a higher incidence in men. Little is known on possible differences in outcome between male and female patients with Thoracic Aortic Aneurysm (TAA). Aortic disease is thought to affect men more frequently than women, and aortic growth is different between men and women. Current data suggest that women are at an increased risk of both dying from aortic dissection and having aorta-related complications compared to men (1). The mechanisms for these male-female difference in TAA outcome remain, however, unclear. The timing of preventive surgery is now not different for men and women, but gender-based cut-off values for maximal aortic diameter based on differences in vessel wall composition might be needed.

Detailed Description
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Thoracic aortic aneurysms (TAA) result from progressive dilatation of the thoracic aorta and confer a risk for aortic dissection or rupture, which is associated with significant morbidity and mortality. In the Netherlands there are an estimated 200.000 adults with TAA, and annually 600 deaths after aortic dissection or rupture. There are clear differences in the incidence of TAA between men and women, with a higher incidence in men. Little is known on possible differences in outcome between male and female patients with Thoracic Aortic Aneurysm (TAA). Aortic disease is thought to affect men more frequently than women, and aortic growth is different between men and women. Current data suggest that women are at an increased risk of both dying from aortic dissection and having aorta-related complications compared to men(1). However, the mechanisms for these male-female differences in TAA outcome remain unclear. The timing of preventive surgery is not different for men and women, but gender-based cut-off values for maximal aortic diameter based on differences in vessel wall composition might be beneficial for outcome. The current research project aims to implement male-female specific insights into aortic root and ascending aorta characteristics into clinical practice, allowing better identification of high risk Thoracic Aortic Aneurysm (TAA) patients and better timing of intervention. With this study the investigators aim to obtain insight into male-female differences in the immunohistological and biomechanical properties of the thoracic aortic wall. In order to reveal possible mechanisms for male-female differences in TAA.

Official Title
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Male-female Differences in Immunohistological and Biomechanical Properties of the Thoracic Aorta

Conditions
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Thoracic Aortic Aneurysm

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (≥ 18 years old) who have a thoracic aortic aneurysm and are scheduled for elective thoracic aortic surgery in the Erasmus MC or the LUMC. Exclusion Criteria: Patients with a known connective tissue disease (e.g. Marfan Syndrome and Ehlers-Danlos syndromes). Connective tissue disease,

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sample collection aortic tissue<br>Sample collection thoracic aorta tissue | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Male-female differences in immunohistochemical and mass spectrometry-based estrogen and testosterone receptor expression levels (and density) in the proximal aortic wall | To investigate male-female differences in estrogen receptor (ESR-alpha and ESRbeta) and testosterone receptor (AR) tissue expression in the wall of the aortic root and ascending aorta by immunohistochemical techniques and mass spectometry. Comparisons will be made using a students t-test. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Male-female differences in immunohistochemical or mass spectrometry-based sex hormone receptor expression levels (and density) in the proximal aortic wall. | To perform an explorative analysis of differences in sex hormone receptor expression in the relation to 1) the immunohistological properties of the aortic wall structure (smooth muscle cell differentiation, presence of macrophages, endothelial cell activation and extracellular matrix, through the following markers: alpha smooth muscle actin, sex hormone receptors (ESR1, RAGE, MMP 2, 3 and 9 and aromatase expression as marker for estrogen synthesis in SMC in both male and female), presence of macrophages (CD68 and MAC2) and endothelial cell activation (NOS3, TGF-β signaling) and extracellular matrix (a.o. fibrillin 1, elastin, collagen and crosslinking)) and to (1) sex hormone (androstenedione, DHEA, testosterone and SHBG in nmol/L, LH and FSH in IU/L, DHEA-S in micromole/L, AMH in micrograms/L, estradiol in picomol/L) and sRAGE (picograms/L) levels in blood, (2) aortic diameter (in millimeters) and (3) age (in years) using linear regression models. | 1 year |