Response of plasma matrix metalloproteinase-9 to conventional abdominal aortic aneurysm repair or endovascular exclusion: implications for endoleak.

PURPOSE Matrix metalloproteinases are enzymes capable of breaking down all of the components of the extracellular matrix and have been implicated in the development of aneurysm formation. Because matrix metalloproteinase-9 (MMP-9) levels are elevated in aortic aneurysmal tissue and in that patient plasma, we hypothesized that plasma MMP-9 levels should decrease significantly after conventional and endovascular infrarenal abdominal aortic aneurysm (AAA) repair but that plasma MMP-9 levels would remain elevated in patients with endoleaks. METHODS A sandwich enzyme-linked immunosorbent assay was used to measure plasma levels of MMP-9 in patients with AAA who underwent conventional (n = 26; mean age, 71.5 years) and endovascular (n = 25; mean age, 76.4 years) AAA repair. Levels were drawn before surgery and at 1 month and 3 months after surgery. Eight patients for endovascular repair had endoleaks identified on postoperative computed axial tomographic scans. RESULTS No correlation existed between preoperative plasma MMP-9 levels when compared with age, gender, or aneurysm diameter. No significant difference in preoperative plasma MMP-9 levels or AAA diameter was identified between patients with conventional repair compared with endovascular repair. Of the 51 patients, 33 had follow-up samples available for analysis. A significant increase in mean plasma MMP-9 levels was noted 1 month (149.5 +/- 40.1 ng/mL) after conventional AAA repair compared with preoperative levels (83.9 +/- 26.1 ng/mL; P <.05) and remained elevated 3 months after surgery (129.8 +/- 56.6 ng/mL). In those patients who underwent endovascular aneurysm exclusion without endoleak, a significant decrease in mean plasma MMP-9 levels was noted at 3 months (27.4 +/- 5.2 ng/mL) when compared with preoperative values (60.8 +/- 8.8 ng/mL; P <.01). In contrast, patients with endoleak after endovascular exclusion did not have a significant decrease in plasma MMP-9 levels at 3 months. CONCLUSION Plasma MMP-9 levels remain elevated for as much as 3 months after conventional AAA repair, whereas successful endovascular exclusion of an AAA results in decreased plasma MMP-9 levels by 3 months. MMP-9 may have clinical value as an enzymatic marker for endoleak after endovascular AAA exclusion.

[1]  J. Parodi,et al.  Neutrophil Respiratory Burst Activity and Pro- and Anti-inflammatory Cytokines in AAA Surgery: Conventional versus Endoluminal Treatment , 2001, Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists.

[2]  S. Friedman The 50th anniversary of abdominal aortic reconstruction. , 2001, Journal of vascular surgery.

[3]  D. Hovsepian,et al.  Elevated plasma levels of matrix metalloproteinase-9 in patients with abdominal aortic aneurysms: a circulating marker of degenerative aneurysm disease. , 2000, Journal of vascular and interventional radiology : JVIR.

[4]  J. Lindholt,et al.  The plasma level of matrix metalloproteinase 9 may predict the natural history of small abdominal aortic aneurysms. A preliminary study. , 2000, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[5]  B. Kelley,et al.  Accelerated replicative senescence of medial smooth muscle cells derived from abdominal aortic aneurysms compared to the adjacent inferior mesenteric artery. , 2000, The Journal of surgical research.

[6]  S. Shapiro,et al.  Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms. , 2000, The Journal of clinical investigation.

[7]  J. Lundbom,et al.  The inflammatory response following treatment of abdominal aortic aneurysms: a comparison between open surgery and endovascular repair. , 2000, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[8]  Rodney A. White,et al.  Aneurysm rupture after endovascular repair using the AneuRx stent graft. , 2000, Journal of vascular surgery.

[9]  B. Rubin,et al.  Preoperative treatment with doxycycline reduces aortic wall expression and activation of matrix metalloproteinases in patients with abdominal aortic aneurysms. , 2000, Journal of vascular surgery.

[10]  D. Sumner,et al.  Algorithm for the diagnosis and treatment of endoleaks. , 1999, American journal of surgery.

[11]  P. Libby,et al.  Plasma concentrations of interleukin-6 and abdominal aortic diameter among subjects without aortic dilatation. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[12]  B. Baxter,et al.  MMP Inhibition in Abdominal Aortic Aneurysms: Rationale for a Prospective Randomized Clinical Trial , 1999, Annals of the New York Academy of Sciences.

[13]  B. Starcher,et al.  Suppression of experimental abdominal aortic aneurysms by systemic treatment with a hydroxamate-based matrix metalloproteinase inhibitor (RS 132908). , 1999, Journal of vascular surgery.

[14]  L. Golub,et al.  Pharmacologic suppression of experimental abdominal aortic aneurysms: acomparison of doxycycline and four chemically modified tetracyclines. , 1998, Journal of vascular surgery.

[15]  W. Frishman,et al.  Matrix Metalloproteinases and Abdominal Aortic Aneurysms: A Potential Therapeutic Target , 1998, Journal of clinical pharmacology.

[16]  B. Baxter,et al.  FORMATION of aneurysms. , 1998, Lancet.

[17]  M. Leinonen,et al.  Elevated circulating levels of inflammatory cytokines in patients with abdominal aortic aneurysm. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[18]  W. Pearce,et al.  Size matters: the relationship between MMP-9 expression and aortic diameter. , 1997, Circulation.

[19]  W. Pearce,et al.  Expression of matrix metalloproteinases and their inhibitors in aneurysms and normal aorta. , 1997, Surgery.

[20]  W. Pearce,et al.  Cellular Components and Features of Immune Response in Abdominal Aortic Aneurysms a , 1996, Annals of the New York Academy of Sciences.

[21]  A. Ghorpade,et al.  Biochemistry and Molecular Regulation of Matrix Macromolecules in Abdominal Aortic Aneurysms , 1996, Annals of the New York Academy of Sciences.

[22]  K. V. Reddy,et al.  Role of Serine Proteases in Aneurysm Development a , 1996, Annals of the New York Academy of Sciences.

[23]  W. Parks,et al.  Role of Matrix Metalloproteinases in Abdominal Aortic Aneurysms a , 1996, Annals of the New York Academy of Sciences.

[24]  W. Parks,et al.  Doxycycline inhibition of aneurysmal degeneration in an elastase-induced rat model of abdominal aortic aneurysm: preservation of aortic elastin associated with suppressed production of 92 kD gelatinase. , 1996, Journal of vascular surgery.

[25]  J. Powell,et al.  Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[26]  W. Pearce,et al.  In situ localization and quantification of mRNA for 92-kD type IV collagenase and its inhibitor in aneurysmal, occlusive, and normal aorta. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[27]  R. Mecham,et al.  Production and localization of 92-kilodalton gelatinase in abdominal aortic aneurysms. An elastolytic metalloproteinase expressed by aneurysm-infiltrating macrophages. , 1995, The Journal of clinical investigation.

[28]  J. Scholes,et al.  Cellular localization of matrix metalloproteinases in the abdominal aortic aneurysm wall. , 1994, Journal of vascular surgery.

[29]  H. Nagase,et al.  Identification of matrix metalloproteinases 3 (stromelysin-1) and 9 (gelatinase B) in abdominal aortic aneurysm. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[30]  J. Reilly,et al.  Possible key role for plasmin in the pathogenesis of abdominal aortic aneurysms. , 1994, Surgery.

[31]  B. McManus,et al.  Abdominal aortic aneurysms are associated with altered matrix proteins of the nonaneurysmal aortic segments. , 1994, Journal of vascular surgery.

[32]  R. Busuttil,et al.  A new serum proteolytic enzyme in aneurysm pathogenesis. , 1985, Journal of vascular surgery.

[33]  R. Busuttil,et al.  Elastase activity: the role of elastase in aortic aneurysm formation. , 1982, The Journal of surgical research.

[34]  W. Pearce,et al.  Increased plasma levels of metalloproteinase-9 are associated with abdominal aortic aneurysms. , 1999, Journal of vascular surgery.

[35]  J. Scholes,et al.  Matrix metalloproteinases in abdominal aortic aneurysm: characterization, purification, and their possible sources. , 1994, Connective tissue research.