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Ann Thorac Surg 2004;78:2106-2110
© 2004 The Society of Thoracic Surgeons

Original Article: Cardiovascular

Increased Tissue Microarray Matrix Metalloproteinase Expression Favors Proteolysis in Thoracic Aortic Aneurysms and Dissections

George J. Koullias, MD, PhDa, Pars Ravichandran, MDb, Dimitris P. Korkolis, MD, PhDa, David L. Rimm, MDc, John A. Elefteriades, MDa,*

a Section of Cardiothoracic Surgery
b Department of Surgical Pathology
c Yale Microarray Facility, Yale New Haven Hospital, New Haven, Connecticut, USA

Accepted for publication May 6, 2004.

* Address reprint requests to Dr Elefteriades, Section of Cardiothoracic Surgery, Yale University School of Medicine, New Haven, CT 06510 (E-mail: john.elefteriades{at}yale.edu).

BACKGROUND: Little information is available regarding the role of matrix metalloproteinases (MMPs) in thoracic aortic aneurysms and dissections. We applied tissue microarray analysis to determine MMP profiles in a large group of surgically resected thoracic aneurysms and dissections.

METHODS: Specimens from 47 patients undergoing a variety of surgical procedures for thoracic aneurysm (n = 30) and dissection (n = 17) were included. Expression of MMP-1, MMP-2, and MMP-9 and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were assessed by aortic tissue microarray immunostaining. Matrix metalloproteinase and TIMP expression in aortic tissue was compared with seven control aortic specimens, free of any vascular disease.

RESULTS: Expression of MMP-1 and MMP-9 was significantly increased in aneurysm and aortic dissection patients compared with control specimens (p < 0.05). Expression of TIMP-2 was significantly increased in the entire patient group, compared with control specimens (p < 0.05). Aortic dissection patients had higher MMP-2 and MMP-9 expression than aortic aneurysm patients in areas of disease. Compared with control patients, the MMP-9 to TIMP-1 ratio (a relative index of proteolytic state) was increased in both the aortic aneurysm and dissection groups (p < 0.05).

CONCLUSIONS: The increased MMP expression in aortic aneurysms and dissections indicates a metamorphosis in the aneurysm wall toward increased proteolysis compared with the normal aorta. Furthermore, we find even higher MMP-2 and MMP-9 presence in aortic dissection. In both aneurysms and dissections, this transformation to a proteolytic state likely plays an important pathophysiologic role in the development and progression of the aortic disease. The recognition of this pathophysiologic mechanism raises the potential for drug therapy to interrupt the cascade of events.


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