Cardiac alterations in cancer-induced cachexia in mice.
Cachexia is a common syndrome in advanced cancer patients and causes up to 22% of cancer-related deaths. It remains elusive whether cancer cachexia causes heart failure. We investigated the effect of cancer cachexia on heart function and cardiac muscle structure in a mouse model. Male CD2F1 mice were inoculated with either colon-26 adenocarcinoma cells (Tumor group) or vehicle (PBS) (No Tumor group and Pair-fed group). Heart function as measured by fractional shortening in vivo using transthoracic echocardiography was performed on day 14 after tumor or PBS inoculation. At necropsy (day 17), hearts were collected for histology, transmission electron microscopy, RT-PCR and SDS-PAGE analysis. Mice from the Tumor group displayed a significantly reduced fractional shortening compared to mice in the No Tumor and Pair-fed groups. In hearts of the Tumor mice compared to the other groups, there was marked fibrosis and transmission electron microscopy revealed disrupted myocardial ultrastructure. Gene expression of troponin I, a regulator of cardiac muscle contraction, was reduced. Moreover, both mRNA and protein levels of myosin heavy chain (MHC) were altered whereby MHCalpha (adult isoform) was decreased and MHCbeta (fetal isoform) was increased indicating reactivation of the fetal gene expression pattern. In conclusion, heart function was diminished in mice with tumor-induced cachexia, and this impaired function was associated with increased fibrosis, disrupted myocardial structure and altered composition of contractile proteins of cardiac muscle.
Tian
Min
M
Department of Human Nutrition, College of Education and Human Ecology, The Ohio State University, Columbus, OH 43210, USA.
Nishijima
Yoshinori
Y
Asp
Michelle L
ML
Stout
Michael B
MB
Reiser
Peter J
PJ
Belury
Martha A
MA
D000230:Adenocarcinoma / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001835:Body Weight; D002100:Cachexia / Q000150:complications / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D002319:Cardiovascular System / Q000503:physiopathology; D003110:Colonic Neoplasms / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D003285:Contractile Proteins / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D006331:Heart Diseases / Q000209:etiology* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009369:Neoplasms / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D047368:Tumor Burden
D003285:Contractile Proteins; D016207:Cytokines; D018836:Inflammation Mediators