The lack of cardiotrophin-1 alters expression of interleukin-6 and leukemia inhibitory factor mRNA but does not impair cardiac injury response.
Cardiotrophin-1 (CT-1) was identified as a growth factor for cardiac myocytes and CT-1 protects myocytes from cell death. Adult CT-1(-/-) mice exhibit neural deficits including the loss of preganglionic sympathetic neurons, but their autonomic and cardiac parameters have not been examined. We used these mice to determine if the absence of CT-1 or loss of preganglionic sympathetic input altered heart rate, left ventricular pressure, cardiac contractility (dP/dt), or cell death following ischemia-reperfusion. Basal heart rate was increased in CT-1(-/-) mice, and this difference was abolished by ganglionic block. Left ventricular pressure and dP/dt were unchanged. Dobutamine stimulated similar increases in heart rate and dP/dt in both genotypes, but ventricular pressure was significantly lower in CT-1 nulls. Cardiac expression of interleukin-6 (IL-6) mRNA was increased significantly in CT-1 null mice, while leukemia inhibitory factor (LIF) mRNA was unchanged. Infarct size normalized to area at risk was no different in CT-1(-/-) mice (33.8+/-1.0% vs. 37.7+/-3.2% WT) 24h after ischemia-reperfusion. Induction of IL-6 mRNA after infarct was significantly abrogated in CT-1 null mice compared to wild-type mice, but LIF mRNA-induction remained significant in CT-1 null mice and might contribute to cardiac protection in the absence of CT-1.
Gritman
Kurt
K
Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97239, USA.
Van Winkle
Donna M
DM
Lorentz
Christina U
CU
Pennica
Diane
D
Habecker
Beth A
BA
D000818:Animals; D001835:Body Weight; D016207:Cytokines / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006335:Heart Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate; D015850:Interleukin-6 / Q000235:genetics*; D053605:Leukemia Inhibitory Factor / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics
D016207:Cytokines; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D012333:RNA, Messenger; C092073:cardiotrophin 1