Background & aims: Cardiotrophin-1 (CT-1), a cytokine belonging to the interleukin-6 family, exerts proliferative and secretory effects in vascular smooth muscle cells. We aimed to investigate the functional and morphological vascular changes induced by chronic CT-1 administration in rats and its involvement in the arterial phenotype of CT-1-null mice.

Methods: A) CT-1 (20μg/Kg, IP) was administrated to Wistar rats for six weeks (n=10/group). B) 2 year-old wild-type (WT) (n=12) and CT-1-null mice (n=12) were studied. Vascular structure and function were evaluated by an echo-tracking device. Circumferential wall stress, incremental elastic modulus (Einc), media cross-sectional area and pulse wave velocity (PWV) were measured. Aortic wall collagen, elastin and fibronectin contents were determined using immunohistochemistry, RT-PCR and Western blot.

Results: A) Neither vehicle nor CT-1 treatment modified BP. The Einc/wall stress curve from CT-1-treated was shifted to the left as compared with vehicle group. CT-1-treated rats also showed increased media cross sectional area (p<0.01), collagen content (p<0.01) and fibronectin expression (p<0.01). B) CT-1-null mice presented an increased wall stress (p<0.05) and Einc (p<0.05) as compared with WT mice. Media cross sectional area, collagen and fibronectin content were reduced (p<0.05) in mice lacking CT-1.

Conclusions: Normotensive rats subjected to CT-1 overloading developed impaired vascular function, characterized by an increment in arterial stiffness accompanied by an augmented media thickness and extracellular matrix production. Accordingly, CT-1-null mice presented a reduced arterial stiffness and a reduced media thickness and collagen content. Our data show that CT-1 is a key player in arterial thickness and stiffness.