This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ikonomidis, J. S. Articles by Gorman, R. C. Search for Related Content PubMed PubMed Citation Articles by Ikonomidis, J. S. Articles by Gorman, R. C. Related Collections Aneurysm, AVM, hematoma CV surgery: aortic and vascular disease Cell signalling/signal transduction Growth factors/cytokines

(Circulation. 2006;114:I-365 – I-370.)
© 2006 American Heart Association, Inc.

Surgery for Aortic and Peripheral Vascular Disease

Expression of Matrix Metalloproteinases and Endogenous Inhibitors Within Ascending Aortic Aneurysms of Patients With Marfan Syndrome

John S. Ikonomidis, MD, PhD; Jeffery A. Jones, PhD; John R. Barbour, MD; Robert E. Stroud, MS; Leslie L. Clark, MSc; Brooke S. Kaplan, BSc; Ahmed Zeeshan, MD; Joseph E. Bavaria, MD; Joseph H. Gorman, III, MD; Francis G. Spinale, MD, PhD; Robert C. Gorman, MD

From Cardiothoracic Surgical Research (J.S.I., J.A.J, J.R.B., R.E.S., L.L.C., B.S.K., F.G.S.), Division of Cardiothoracic Surgery, Medical University of South Carolina, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC; Division of Cardiothoracic Surgery (A.Z., J.E.B., J.H.G., R.C.G.), University of Pennsylvania, Philadelphia, Pa.

Correspondence to John S. Ikonomidis, Associate Professor of Surgery, Division of Cardiothoracic Surgery, Medical University of South Carolina, Suite 409 CSB, 96 Jonathan Lucas St, Charleston, SC 29425. E-mail ikonomij{at}musc.edu

Background— Marfan syndrome (MFS) is known to cause ascending thoracic aortic aneurysms (ATAAs). Transforming growth factor beta (TGF-ß) has recently been implicated in this process. Imbalances between the matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) have also been shown to contribute to aneurysm formation. Whether and to what degree MMP, TIMP, and TGF-ß signaling profiles are altered in ATAAs in MFS compared with non-MFS patients remains unknown.

Methods and Results— ATAA samples taken during aortic replacement from age-matched MFS (n=9) and non-MFS (n=18) patients were assessed for representative subtypes of all MMP classes, all 4 known TIMPs, and type 2 TGF-ß receptors (TGFBR2). Results were expressed as a percentage (mean±SEM) of reference control samples (100%; n=18) obtained from patients without ATAA. In MFS, decreased MMP-2 (76±7; P<0.05 versus control), increased MMP-12 (161±27% versus control; P<0.05), and increased MT1-MMP (248±64% versus 91±21 non-MFS and control; P<0.05) were observed. TIMP-3 (74±23%) was reduced compared with control values (P<0.05) and TIMP-2 was elevated (128±31%) compared with non-MFS (73±19%; P<0.05). In non-MFS samples, MMP-1 (70±16%), MMP-3 (77±18%), MMP-8 (75±11%), MMP-9 (69±14%), and MMP-12 (85±15%) were decreased compared with control (P<0.05). TIMPs 1 to 3 were reduced in non-MFS compared with control values (P<0.05). TGFBR2 were increased in MFS (193±32%) compared with non-MFS (95±16%) and controls (P<0.05).

Conclusions— A unique MMP and TIMP portfolio was observed in ATAAs from MFS compared with non-MFS patients. In addition, MFS samples showed evidence of increased TGF-ß signaling. These differences suggest disparate mechanisms of extracellular matrix remodeling between these 2 groups of patients.

Key Words: aneurysm • aorta • Marfan • MMP • TIMP