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Metalloproteinase expression is altered in cardiac and skeletal muscle in cancer cachexia
- Source :
- American Journal of Physiology-Heart and Circulatory Physiology. 309:H685-H691
- Publication Year :
- 2015
- Publisher :
- American Physiological Society, 2015.
-
Abstract
- Cardiac and skeletal muscle dysfunction is a recognized effect of cancer-induced cachexia, with alterations in heart function leading to heart failure and negatively impacting patient morbidity. Cachexia is a complex and multifaceted disease state with several potential contributors to cardiac and skeletal muscle dysfunction. Matrix metalloproteinases (MMPs) are a family of enzymes capable of degrading components of the extracellular matrix (ECM). Changes to the ECM cause disruption both in the connections between cells at the basement membrane and in cell-to-cell interactions. In the present study, we used a murine model of C26 adenocarcinoma-induced cancer cachexia to determine changes in MMP gene and protein expression in cardiac and skeletal muscle. We analyzed MMP-2, MMP-3, MMP-9, and MMP-14 as they have been shown to contribute to both cardiac and skeletal muscle ECM changes and, thereby, to pathology in models of heart failure and muscular dystrophy. In our model, cardiac and skeletal muscles showed a significant increase in RNA and protein levels of several MMPs and tissue inhibitors of metalloproteinases. Cardiac muscle showed significant protein increases in MMP-2, MMP-3, MMP-9, and MMP-14, whereas skeletal muscles showed increases in MMP-2, MMP-3, and MMP-14. Furthermore, collagen deposition was increased after C26 adenocarcinoma-induced cancer cachexia as indicated by an increased left ventricular picrosirius red-positive-stained area. Increases in serum hydroxyproline suggest increased collagen turnover, implicating skeletal muscle remodeling. Our findings demonstrate that cancer cachexia-associated matrix remodeling results in cardiac fibrosis and possible skeletal muscle remodeling. With these findings, MMPs represent a possible therapeutic target for the treatment of cancer-induced cachexia.
- Subjects :
- medicine.medical_specialty
Cachexia
Physiology
Cardiac fibrosis
Matrix metalloproteinase
Biology
Mice
Integrative Cardiovascular Physiology and Pathophysiology
Physiology (medical)
Internal medicine
medicine
Animals
RNA, Messenger
Muscular dystrophy
Muscle, Skeletal
Mice, Inbred BALB C
Myocardium
Cardiac muscle
Skeletal muscle
Neoplasms, Experimental
medicine.disease
Matrix Metalloproteinases
medicine.anatomical_structure
Endocrinology
Mice, Inbred DBA
Heart failure
Female
Cardiology and Cardiovascular Medicine
ITGA7
Subjects
Details
- ISSN :
- 15221539 and 03636135
- Volume :
- 309
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Heart and Circulatory Physiology
- Accession number :
- edsair.doi.dedup.....e52dca07cb85122a66c7f4939cbc5f36