TY - JOUR
T1 - Cardiotrophin 1 is involved in cardiac, vascular, and renal fibrosis and dysfunction
AU - López-Andrés, Natalia
AU - Rousseau, Amélie
AU - Akhtar, Riaz
AU - Calvier, Laurent
AU - Iñigo, Carmen
AU - Labat, Carlos
AU - Zhao, Xuegen
AU - Cruickshank, Kennedy
AU - Díez, Javier
AU - Zannad, Faiez
AU - Lacolley, Patrick
AU - Rossignol, Patrick
N1 - Funding Information:
The writers gratefully acknowledge financial support from the China Scholarship Council, the Natural Sciences and Engineering Research Council (NSERC) of Canada, and the Chinese Water Pollution Control Program (Project Number 2011ZX07301-004). The authors also would like to thank Perry Fedun and Yangbo Tang for their technical assistance.
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - arterial stiffness
KW - cardiotrophin 1
KW - fibrosis
KW - renal dysfunction
KW - ventricular function
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U2 - 10.1161/HYPERTENSIONAHA.112.194407
DO - 10.1161/HYPERTENSIONAHA.112.194407
M3 - Article
C2 - 22733458
AN - SCOPUS:84864278283
SN - 0194-911X
VL - 60
SP - 563
EP - 573
JO - Hypertension
JF - Hypertension
IS - 2
ER -