Aims: Cardiotrophin-1 (CT-1), a cytokine belonging to the interleukin-6 family, exerts proliferative and secretory effects in vascular smooth muscle cells. We investigated the morphological, micromechanical and molecular vascular changes induced by chronic CT-1 administration in rats.

Methods: Recombinant rat CT-1 (20 μg/Kg, IP) or vehicle (n=10/group) was administrated to Wistar rats for six weeks. Vascular structure and function were determined with an echo-tracking device. Aortic extracellular matrix (ECM) protein production and attachments were quantified by immunohistochemistry, RT-PCR and Western blot. Acoustic wavespeed within the aorta was determined using a novel scanning acoustic microscopy (SAM) method at 1 GHz which enables tissues stiffness to be determined with a ∼1 μm spatial resolution.

Results: In normotensive CT-1-treated rats, the incremental elastic modulus-circumferential wall stress curve was shifted leftward compared to vehicle, indicating increased arterial stiffness. Aortic media thickness was higher (40%) in CT-1-treated rats. Aortic collagen type I (80%), fibronectin (80%), metalloproteinases activities (40%), integrins (70%) and focal adhesion proteins (60%) were also increased in whereas elastin levels were similar to controls. Further, increased acoustic wavespeed in CT-1 rats (1694 ± 2 ms⁻¹ compared to 1673 ± 2 ms⁻¹, p<0.001) was found in parallel with increases in collagen volume fraction (21 % as compared to 9 % in controls).

Conclusions: We demonstrate that CT-1 is a key player in arterial remodelling and stiffness by modulating aortic mechanical properties, media thickness, ECM production and attachments. Thus, CT-1 could be a new biotarget to reduce arterial stiffness and decrease ECM deposition in vascular diseases.