Background: Untreated thoracic aortic aneurysm disease (TAAD) can lead to acute type A aortic dissection (ATAD), an often-fatal condition where a tear develops between layers of the aortic wall. Careful balance of ATAD risk vs. surgical risks is paramount to determining the best surgical timing for each patient, and we lack an adequately sensitive marker of ATAD risk. Turning our attention to biomarkers, our lab has employed a tissue-first discovery approach to identify candidate proteins in aortic tissue obtained from patients with TAAD, dissection, and healthy controls, with subsequent validation in blood. Through global and phospho-proteomics, we have identified proteins that deserve further exploration of mechanisms through in vitro and in vivo models. Additionally, we are analysing plasma from patients under TAAD surveillance to determine how levels of these proteins change in patients whose aneurysms grow compared to those with stable aneurysms.
Scientific rationale: This project focuses on clinical translation by measuring these proteins in plasma to assess quantitative changes as ATAD risk changes, with external validation by comparing results from our internal study to plasma proteomic data from the UK Biobank.
Objectives:
a. Determine the reference ranges in plasma for these candidate proteins in non-TAAD participants, and how they are influenced by clinical factors such as age, sex, ethnicity, and cardiovascular diseases (eg: hypertension, hypercholesterolaemia).
b. Compare levels of these candidate proteins in TAAD vs non-TAAD participants. We will perform additional subgroup analyses for relevant clinical factors, including age, sex, menopausal status, genetic variants, cardiovascular disease, and smoking history.
c. For UKB participants with repeat plasma proteomic results, we will compare levels of these candidate proteins at baseline vs. subsequent testing to assess how levels change over time with respect to aneurysm size.
