Minocycline attenuates cardiac dysfunction in tumor-burdened mice
| Autor: | Clayton M. Eichenseer, Loren E. Wold, Raymond D. Devine |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Cardiac function curve
Pathology medicine.medical_specialty Cachexia Heart Diseases Gene Expression Minocycline 030204 cardiovascular system & hematology Pharmacology Matrix metalloproteinase Article Extracellular matrix 03 medical and health sciences Electrocardiography Mice 0302 clinical medicine Neoplasms medicine Animals Myocytes Cardiac Calcium Signaling Systole Molecular Biology Tissue Inhibitor of Metalloproteinase-1 business.industry Cancer medicine.disease Matrix Metalloproteinases Extracellular Matrix Disease Models Animal medicine.anatomical_structure Ventricle Calcium Female Collagen Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery medicine.drug Muscle Contraction |
| Zdroj: | Journal of molecular and cellular cardiology. 100 |
| ISSN: | 1095-8584 |
| Popis: | Cardiovascular dysfunction as a result of tumor burden is becoming a recognized complication; however, the mechanisms remain unknown. A murine model of cancer cachexia has shown marked increases of matrix metalloproteinases (MMPs), known mediators of cardiac remodeling, in the left ventricle. The extent to which MMPs were involved in remodeling remained obscured. To this end a common antibiotic, minocycline, with MMP inhibitory properties was used to elucidate MMP involvement in tumor induced cardiovascular dysfunction. Tumor-bearing mice showed decreased cardiac function with reduced posterior wall thickness (PWTs) during systole, increased MMP and collagen expression consistent with fibrotic remodeling. Administration of minocycline preserved cardiac function in tumor bearing mice and decreased collagen RNA expression in the left ventricle. MMP protein levels were unaffected by minocycline administration, with the exception of MMP-9, indicating minocycline inhibition mechanisms are directly affecting MMP activity. Cancer induced cardiovascular dysfunction is an increasing concern, novel therapeutics are needed to prevent cardiac complications. Minocycline is a well-known antibiotic and recently has been shown to possess MMP inhibitory properties. Our findings presented here show that minocycline could represent a novel use for a long established drug in the prevention and treatment of cancer induced cardiovascular dysfunction. |
| Databáze: | OpenAIRE |
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