Minocycline attenuates cardiac dysfunction in tumor-burdened mice.
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 are involved in remodeling remains 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.
Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, United States; Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH, United States.
Raymond D
RD
Devine
Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
Clayton M
CM
Eichenseer
Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, United States; Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, United States; College of Nursing, The Ohio State University, Columbus, OH, United States. Electronic address: Loren.Wold@osumc.edu.
Loren E
LE
Wold
D000818:Animals; D002100:Cachexia / Q000150:complications / Q000209:etiology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004562:Electrocardiography; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006331:Heart Diseases / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008911:Minocycline / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000150:complications*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D020782:Matrix Metalloproteinases; D008911:Minocycline; D002118:Calcium
Cancer cachexia; Cardiomyocyte; Extracellular matrix; Matrix metalloproteinase; Minocycline; Tissue inhibitors of matrix metalloproteinase
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