6 research outputs found
Absence of cardiotrophin 1 is associated with decreased age-dependent arterial stiffness and increased longevity in mice
Cardiotrophin 1 (CT-1), an interleukin 6 family member, promotes fibrosis and arterial stiffness. We hypothesized
that the absence of CT-1 influences arterial fibrosis and stiffness, senescence, and life span. In senescent 29-month-
old mice, vascular function was analyzed by echotracking device. Arterial histomorphology, senescence, metabolic,
inflammatory, and oxidative stress parameters were measured by immunohistochemistry, reverse transcription polymerase
chain reaction, Western blot, and ELISA. Survival rate of wild-type and CT-1–null mice was studied. Vascular smooth
muscle cells were treated with CT-1 (10
−9
mol/L) for 15 days to analyze senescence. The wall stress-incremental elastic
modulus curve of old CT-1–null mice was shifted rightward as compared with wild-type mice, indicating decreased
arterial stiffness. Media thickness and wall fibrosis were lower in CT-1–null mice. CT-1–null mice showed decreased
levels of inflammatory, apoptotic, and senescence pathways, whereas telomere-linked proteins, DNA repair proteins,
and antioxidant enzyme activities were increased. CT-1–null mice displayed a 5-month increased median longevity
compared with wild-type mice. In vascular smooth muscle cells, chronic CT-1 stimulation upregulated apoptotic and
senescence markers and downregulated telomere-linked proteins. The absence of CT-1 is associated with decreased
arterial fibrosis, stiffness, and senescence and increased longevity in mice likely through downregulating apoptotic,
senescence, and inflammatory pathways. CT-1 may be a major regulator of arterial stiffness with a major impact on the
aging proces
Cardiotrophin 1 is involved in cardiac, vascular, and renal fibrosis and dysfunction
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 g/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
Absence of cardiotrophin 1 is associated with decreased age-dependent arterial stiffness and increased longevity in mice
Cardiotrophin 1 (CT-1), an interleukin 6 family member, promotes fibrosis and arterial stiffness. We hypothesized
that the absence of CT-1 influences arterial fibrosis and stiffness, senescence, and life span. In senescent 29-month-
old mice, vascular function was analyzed by echotracking device. Arterial histomorphology, senescence, metabolic,
inflammatory, and oxidative stress parameters were measured by immunohistochemistry, reverse transcription polymerase
chain reaction, Western blot, and ELISA. Survival rate of wild-type and CT-1–null mice was studied. Vascular smooth
muscle cells were treated with CT-1 (10
−9
mol/L) for 15 days to analyze senescence. The wall stress-incremental elastic
modulus curve of old CT-1–null mice was shifted rightward as compared with wild-type mice, indicating decreased
arterial stiffness. Media thickness and wall fibrosis were lower in CT-1–null mice. CT-1–null mice showed decreased
levels of inflammatory, apoptotic, and senescence pathways, whereas telomere-linked proteins, DNA repair proteins,
and antioxidant enzyme activities were increased. CT-1–null mice displayed a 5-month increased median longevity
compared with wild-type mice. In vascular smooth muscle cells, chronic CT-1 stimulation upregulated apoptotic and
senescence markers and downregulated telomere-linked proteins. The absence of CT-1 is associated with decreased
arterial fibrosis, stiffness, and senescence and increased longevity in mice likely through downregulating apoptotic,
senescence, and inflammatory pathways. CT-1 may be a major regulator of arterial stiffness with a major impact on the
aging proces