This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Orlandi, A. Articles by Spagnoli, L. G. Search for Related Content PubMed PubMed Citation Articles by Orlandi, A. Articles by Spagnoli, L. G.

(American Journal of Pathology. 2005;166:1619-1628.)
© 2005 American Society for Investigative Pathology

Increased Expression and Activity of Matrix Metalloproteinases Characterize Embolic Cardiac Myxomas

Augusto Orlandi^*, Alessandro Ciucci^*, Amedeo Ferlosio^*, Antonio Pellegrino, Luigi Chiariello and Luigi Giusto Spagnoli^*

From the Departments of Anatomic Pathology^* and Cardiovascular Surgery, Tor Vergata University, Rome, Italy

Tumor embolism occurs in 30 to 50% of all cases of cardiac myxoma, but the causes are still uncertain. Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade the extracellular matrix (ECM) and play a crucial role in plaque instability and aortic aneurysm development, in addition to cancer and heart failure. To determine whether MMP activity contributes to tumor embolism, we examined 27 left atrium-sided myxomas, 10 of which showed clinical signs of peripheral embolism. Immunohistochemistry (in all cases) and Western blotting, and in situ and in-gel zymography (in four embolic and six nonembolic consecutive tumors) demonstrated higher expression and activity of MT1-MMP, pro-MMP-2, and pro-MMP-9 in embolic myxomas, whereas pro-MMP-1, MMP-3, and TIMP-1 levels were similar to those of nonembolic tumors. Reverse transcriptase-polymerase chain reaction demonstrated that increased MMP activity was due, at least in part, to increased transcription and that TIMP-2 transcripts increased in embolic myxomas. In vitro, embolic tumor cells retained higher MT1-MMP and pro-MMP-2 levels in basal conditions and after stimulation with interleukin-1ß and interleukin-6. Increased MMP synthesis and release correlated with enhanced ECM degradation products containing glycosaminoglycan chains in embolic myxoma tissue. Our results strongly suggest that MMP overexpression may contribute to an excessive degradation of tumor ECM and increase the risk of embolism in cardiac myxomas.

This article has been cited by other articles:

				G. Thiene, M. Valente, M. Lombardi, and C. Basso CHAPTER 20 Tumours of the Heart ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]