The Aortic Research Group, led by Professor Richmond Jeremy, undertakes both clinical and laboratory research into genetic causes of thoracic aortic aneurysms. Approximately 50,000 Australians, of all ages, have a genetic aneurysm, which are typically asymptomatic until the potentially fatal event of aortic dissection. Detection of affected individuals, understanding of clinical features and discovery of the cell mechanisms of aneurysm formation are key challenges.
The Aortic Group collaborates with the international Montalcino Aortic Consortium to discover new genes causing aneurysm, describe the clinical risk features and monitor the outcomes after surgical repair. The group also conducts novel laboratory research, underpinned by aortic tissue donated by patients undergoing surgery at RPAH for aortic aneurysms. This material is part of the comprehensive tissue collection of the Sydney Heart Bank. Currently, tissue from over 200 patients has been collected and cryopreserved, including patients with Marfan Syndrome (MFS), bicuspid aortic valve, Loey’s-Dietz syndrome, familial TAAD and atherosclerosis. Additionally, blood samples from affected patients are included. The Bank is continuing to grow in scope and is key resource for new research studies.
One current research focus is a study of how changes in regulators of reading of the DNA code affect severity of aortic disease. We have found that alteration of DNA coding inflammatory genes correlates with the severity of cardiovascular disorders in Marfan syndrome, and this work is being expanded to other genetic aortopathies. Other discoveries include altered expression of miRNA molecules. In human vascular smooth muscle cells, changes to the levels of these miRNAs have an effect on pathways essential to vascular smooth muscle cell function and therefore may be contributing to aneurysm formation.
Currently, large-scale analysis of aortic aneurysm tissue samples is underway to investigate over 4500 proteins and genome-wide RNA expression. These studies will shed light on the mechanisms of aneurysm formation, potentially identify markers of progression of aortic disease and also identify new targets for effective treatment intervention.
The Aortic Group also plays an important role in training the next generation of clinicians and researchers, with 3 PhD and 2 MPhil graduate research students and undergraduate medical students included in the program.