The mission of the Thoracic Aortic Research Group (TARGet) is to improve survival and quality of life for people suffering from cardiovascular disease. We perform fundamental (basic and experimental studies in the laboratory), translational (applying discoveries generated during research in the laboratory) and clinical (studying health and illness in people) research.

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The role of molecular biological factors in the development of cardiovascular disease

A bicuspid aortic valve (BAV) is the most prevalent congenital cardiac anomaly, in which the valve has only two leaflets, instead of the normal three. Patients with a BAV have an increased risk of aneurysm formation and the development of an aortic dissection. Vascular smooth muscle cells in both the non- and dilated aortic wall are characterized by a maturation defect in all BAV patients, as compared to patients with a tricuspid aortic valve, which can contribute to inherent developmental susceptibility. Besides structural abnormalities of the vascular wall, a turbulent blood flow, caused by bicuspid valve geometry, could expedite the pathological process in the aortic wall, leading to aortopathy. Although the risk for aortopathy is significant, not all BAV patients experience (acute) aortic complications in their lifespan, highlighting the complexity of the pathogenetic process. Our recent studies have focused on the embryonic development of semilunar valves and the ascending aortic wall. The results highlight that a defect in the embryogenesis could not only explain the development of a malformed aortic valve but also the increased risk for ascending aorta and arch pathology. Our studies conclude that a common defect in early embryogenesis causes the development of a BAV and associated aortopathy.

Cardiogenetics and its role in cardiovascular disease treatment

The large proportion of cardiovascular disease are determined by the genetic make-up of individuals. Studies suggest that inheritance of common genetic variants crucially determine aortic disease. Our current projects focus on ‘genome wide association studies (GWAS)’  and its potential for treating cardiovascular disease. 

Human induced pluripotent stem cell (hiPSC) are an excellent model to study potential drug targets for cardiovascular disease

Most research on cardiovascular disease in the laboratory has till date derived and cultured from aortic tissues that have been removed surgically when reaching end-stage disease thresholds. It is therefore impossible to elucidate the pathophysiology identify possible drug targets by solely studying end-stage tissues as it is hard to distinguish cause-and-effect of the disease process. An excellent model to study an early disease stage and potential drug targets are human induced pluripotent stem cell (hiPSC). HiPSCs can be generated from white blood cells and used in various two and three dimensional (2D and 3D) assays to determine functionality. We are currently developing vascular smooth muscle derived human induced pluripotent stem cells on our laboratory.

Similar characteristics between Marfan syndrome, Bicuspid Aortic Valve and Aortic Dissection disease

A thoracic aortic dissection is a serious complication which is more often seen in patients with Marfan syndrome and patients with a bicuspid aortic valve than in individuals with a tricuspid aortic valve. The identification of common pathological mechanisms leading to aortic complications in non-syndromic and syndromic diseases has significantly improved our understanding within the field of personalized treatment strategies in non-syndromic and syndromic conditions.