Serum levels of matrix metalloproteinases 2 and 9 and TGFBR2 gene screening in patients with ascending aortic dilatation.

Development of ascending aortic dilatation (AAD) in about 10 % of patients operated for aortic valve disease (AVD) is probably based on intrinsic pathology of the aortic wall. This may involve an abnormality in the process of extracellular matrix remodelling. The present study evaluated the serum levels of specific metalloproteinases (MMP-2 and MMP-9) and investigated the gene for transforming growth factor receptor 2 (TGFBR2) in 28 patients with AVD associated with AAD (mean age 60.6 years), in 29 patients (68.9 years) with AVD without AAD, and in 30 healthy controls (45.3 years). The serum levels of MMPs were determined by ELISA. Further, we focused on genetic screening of the TGFBR2 gene. Plasma MMP-2 concentrations were significantly higher in the groups of patients compared to the controls: median 1315.0 (mean 1265.2 ± SD 391.3) in AVD with AAD, 1240.0 (1327.8 ± 352.5) in AVD without AAD versus 902.5 (872.3 ± 166.2) ng/ml in the healthy controls, in both cases P < 0.001. The serum levels of MMP-9 were significantly higher in AVD with AAD patients [107.0 (202.3 ± 313.0)] and in AVD without AAD patients [107.0 (185.8 ± 264.3)] compared to the healthy controls [14.5 (21.2 ± 24.8) ng/ml], in both cases P < 0.001. No significant correlation was observed between plasma MMP-2 and MMP-9 and ascending aorta diameter. Genetic screening did not reveal any variation in the TGFBR2 gene in the patients. Measurement of MMP levels is a simple and relatively rapid laboratory test that could be used as a biochemical indicator when evaluated in combination with imaging techniques.

[1]  V. Yong,et al.  Targeting MMPs in acute and chronic neurological conditions , 2007, Neurotherapeutics.

[2]  B. S. Sekhon.  Matrix metalloproteinases – an overview , 2010 .

[3]  C. Foroulis,et al.  Serum levels of matrix metalloproteinases -1,-2,-3 and -9 in thoracic aortic diseases and acute myocardial ischemia , 2009, Journal of cardiothoracic surgery.

[4]  C. Overall,et al.  Matrix metalloproteinase proteomics: substrates, targets, and therapy. , 2009, Current opinion in cell biology.

[5]  S. Lemaire,et al.  Thoracic Aortic Dissection: Are Matrix Metalloproteinases Involved? , 2009, Vascular.

[6]  H. Nagase,et al.  Progress in matrix metalloproteinase research. , 2008, Molecular aspects of medicine.

[7]  Jeffrey A. Jones,et al.  Transforming Growth Factor-β Signaling in Thoracic Aortic Aneurysm Development: A Paradox in Pathogenesis , 2008, Journal of Vascular Research.

[8]  J. Raffetto,et al.  Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease. , 2008, Biochemical pharmacology.

[9]  Andrew J. Ewald,et al.  Matrix metalloproteinases and the regulation of tissue remodelling , 2007, Nature Reviews Molecular Cell Biology.

[10]  S. Shete,et al.  Mutations in Transforming Growth Factor-&bgr; Receptor Type II Cause Familial Thoracic Aortic Aneurysms and Dissections , 2005, Circulation.

[11]  S. Hagl,et al.  Inflammatory regulation of extracellular matrix remodeling in calcific aortic valve stenosis. , 2005, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[12]  Eric M. Isselbacher,et al.  Thoracic and Abdominal Aortic Aneurysms , 2005, Circulation.

[13]  P. Walker,et al.  Abnormal Extracellular Matrix Protein Transport Associated With Increased Apoptosis of Vascular Smooth Muscle Cells in Marfan Syndrome and Bicuspid Aortic Valve Thoracic Aortic Aneurysm , 2003, Circulation.

[14]  B. Strauss,et al.  Vascular matrix remodeling in patients with bicuspid aortic valve malformations: implications for aortic dilatation. , 2003, The Journal of thoracic and cardiovascular surgery.

[15]  D. Arking,et al.  Dysregulation of TGF-β activation contributes to pathogenesis in Marfan syndrome , 2003, Nature Genetics.

[16]  M. Matzuk,et al.  Genetic Analysis of the Mammalian Transforming Growth Factor-β Superfamily , 2002 .

[17]  Timothy C Greiner,et al.  Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. , 2002, The Journal of clinical investigation.

[18]  P. Robinson,et al.  Human Genome and Diseases:¶The molecular pathogenesis of the Marfan syndrome , 2001, Cellular and Molecular Life Sciences CMLS.

[19]  Z. Galis,et al.  Remodeling of Carotid Artery Is Associated With Increased Expression of Matrix Metalloproteinases in Mouse Blood Flow Cessation Model , 2000, Circulation.

[20]  J. Shirani,et al.  Matrix metalloproteinase expression in nonrheumatic aortic stenosis. , 2000, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[21]  T Ishii,et al.  Collagen and elastin degradation by matrix metalloproteinases and tissue inhibitors of matrix metalloproteinase in aortic dissection. , 2000, Human pathology.

[22]  D. Reinhardt,et al.  Mutations in Calcium-binding Epidermal Growth Factor Modules Render Fibrillin-1 Susceptible to Proteolysis , 2000, The Journal of Biological Chemistry.

[23]  K. Tamura,et al.  [Atherosclerosis-related aortic dissection]. , 2000, Kyobu geka. The Japanese journal of thoracic surgery.

[24]  P. Robinson,et al.  The molecular genetics of Marfan syndrome and related microfibrillopathies , 2000, Journal of medical genetics.

[25]  R. E. Luna,et al.  Immunohistochemistry of matrix metalloproteinases and their inhibitors in thoracic aortic aneurysms and aortic valves of patients with Marfan's syndrome. , 1998, Circulation.

[26]  É. Allaire,et al.  Prevention of aneurysm development and rupture by local overexpression of plasminogen activator inhibitor-1. , 1998, Circulation.

[27]  J. Yokota,et al.  Mutation analysis of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human colon cancer using genomic DNA and Intron primers , 1997, Oncogene.

[28]  C. Harris,et al.  The Genomic Structure of the Gene Encoding the Human Transforming Growth Factor β Type II Receptor (TGF-β RII) , 1996 .

[29]  J. McEwan,et al.  Matrix metalloproteinases and cardiovascular disease. , 1995, Circulation research.

[30]  T. Hunter,et al.  The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification 1 , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[31]  P. Libby,et al.  Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. , 1994, The Journal of clinical investigation.

[32]  M. Reidy,et al.  Smooth muscle cell migration and matrix metalloproteinase expression after arterial injury in the rat. , 1994, Circulation research.

[33]  Jeffrey L. Wrana,et al.  Mechanism of activation of the TGF-β receptor , 1994, Nature.

[34]  G. Gibbons,et al.  The emerging concept of vascular remodeling. , 1994, The New England journal of medicine.

[35]  R. Glanville,et al.  Purification and partial characterization of fibrillin, a cysteine-rich structural component of connective tissue microfibrils. , 1991, The Journal of biological chemistry.