Cardiotrophin 1 is involved in cardiac, vascular, and renal fibrosis and dysfunction

Natalia López-Andrés, Amélie Rousseau, Riaz Akhtar, Laurent Calvier, Carmen Iñigo, Carlos Labat, Xuegen Zhao, Kennedy Cruickshank, Javier Díez, Faiez Zannad, Patrick Lacolley, Patrick Rossignol

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Cardiotrophin 1 (CT-1), a cytokine belonging to the interleukin 6 family, is increased in hypertension and in heart failure. We aimed to study the precise role of CT-1 on cardiac, vascular, and renal function; morphology; and remodeling in early stages without hypertension. CT-1 (20 μg/kg per day) or vehicle was administrated to Wistar rats for 6 weeks. Cardiac and vascular functions were analyzed in vivo using M-mode echocardiography, Doppler, and echo tracking device and ex vivo using a scanning acoustic microscopy method. Cardiovascular and renal histomorphology were measured by immunohistochemistry, RT-PCR, and Western blot. Kidney functional properties were assessed by serum creatinine and neutrophile gelatinase-Associated lipocalin and microalbuminuria/creatininuria ratio. Without alterations in blood pressure levels, CT-1 treatment increased left ventricular volumes, reduced fractional shortening and ejection fraction, and induced myocardial dilatation and myocardial fibrosis. In the carotid artery of CT-1-treated rats, the circumferential wall stress-incremental elastic modulus curve was shifted leftward, and the acoustic speed of sound in the aorta was augmented, indicating increased arterial stiffness. Vascular media thickness, collagen, and fibronectin content were increased by CT-1 treatment. CT-1-treated rats presented unaltered serum creatinine concentrations but increased urinary and serum neutrophile gelatinase-Associated lipocalin and microalbuminuria/ creatininuria ratio. This paralleled a glomerular and tubulointerstitial fibrosis accompanied by renal epithelial-mesenchymal transition. CT-1 is a new potent fibrotic agent in heart, vessels, and kidney able to induce cardiovascular-renal dysfunction independent from blood pressure. Thus, CT-1 could be a new target simultaneously integrating alterations of heart, vessels, and kidney in early stages of heart failure.

Original languageEnglish (US)
Pages (from-to)563-573
Number of pages11
Issue number2
StatePublished - Aug 2012
Externally publishedYes


  • arterial stiffness
  • cardiotrophin 1
  • fibrosis
  • renal dysfunction
  • ventricular function

ASJC Scopus subject areas

  • Internal Medicine


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