Aim: Dysfunctional matrix turnover in atherosclerosis and abdominal aortic aneurysm (AAA) leads to the accumulation of tropoelastin rather than cross-linked elastin. We developed a gadolinium-based tropoelastin-specific MR contrast agent (Gd-TESMA) and tested whether quantifying tropoelastin turnover correlates with: i) plaque progression and instability and ii) the rate of aortic aneurysm expansion in experimental models and iii) accumulation of tropoelastin in excised human carotid plaques. 
Methods: Apolipoprotein E-deficient (ApoE-/-) mice with progressive atherosclerosis, New Zealand white rabbits with stable and rupture-prone plaques and angiotensin II (Ang II)-infused ApoE-/- mice with aortic aneurysms we used. In vivo imaging of tropoelastin was performed by administering Gd-TESMA followed by late gadolinium enhancement (LGE) MRI and T1 mapping at 3-Tesla, with subsequent ex vivo validation. 

Results: Screening of different compounds using binding assays showed that the VVGS-based probe discriminated between tropoelastin and cross-linked elastin (asterisk) and bound less to other proteins (Figure 1). Tropoelastin-enhancement  was increased during plaque progression in ApoE-/- mice and decreased with statin-treatment and was verified histologically. Rupture-prone rabbit plaques had higher tropoelastin-enhancement compared with stable plaques. Tropoelastin-enhancement in a murine model of AAA demonstrated that early tropoelastin accumulation correlates with larger subsequent aneurysmal growth. Finally, tropoelastin-enhancement identified accumulation of tropoelastin in excised human carotid plaques.

Conclusions: Tropoelastin-MRI identifies dysfunctional matrix turnover that correlates with plaque progression and instability and with the rate of aneurysm growth. As tropoelastin-MRI identifies tropoelastin accumulation in human tissue, this approach holds promise for improved risk stratification of patients and as a tool to assess novel therapies.

01 - TROPOELASTIN: A NEW IMAGING BIOMARKER OF DYSFUNCTIONAL EXTRACELLULAR MATRIX REMODELLING IN ATHEROSCLEROSIS AND AORTIC ANEURYSM