Cardiotrophin 1 Is Involved in Cardiac, Vascular, and Renal Fibrosis and Dysfunction
- 1 August 2012
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 60 (2), 563-573
- https://doi.org/10.1161/hypertensionaha.112.194407
Abstract
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.Keywords
This publication has 26 references indexed in Scilit:
- A role for cardiotrophin-1 in myocardial remodeling induced by aldosteroneAmerican Journal of Physiology-Heart and Circulatory Physiology, 2011
- Localised micro-mechanical stiffening in the ageing aortaMechanisms of Ageing and Development, 2011
- TGF-β/Smad3 Signaling Promotes Renal Fibrosis by Inhibiting miR-29Journal of the American Society of Nephrology, 2011
- Lipocalin 2 is essential for chronic kidney disease progression in mice and humansJCI Insight, 2010
- Arterial stiffness: a brief reviewActa Pharmacologica Sinica, 2010
- Vascular effects of cardiotrophin-1: a role in hypertension?Journal of Hypertension, 2010
- The Role of Kidney Biopsy in Heart Transplant Candidates With Kidney DiseaseTransplantation, 2010
- Loss of myocardial LIF receptor in experimental heart failure reduces cardiotrophin-1 cytoprotection. A role for neurohumoral agonists?Cardiovascular Research, 2007
- GFP expression in muscle cells impairs actin-myosin interactions: implications for cell therapyNature Methods, 2006
- Increased Carotid Wall Elastic Modulus and Fibronectin in Aldosterone-Salt–Treated RatsCirculation, 2002