PMID- 24746253 OWN - NLM STAT- MEDLINE DCOM- 20140807 LR - 20221207 IS - 1095-8673 (Electronic) IS - 0022-4804 (Print) IS - 0022-4804 (Linking) VI - 189 IP - 2 DP - 2014 Jun 15 TI - Matrix metalloproteinase levels in chronic thoracic aortic dissection. PG - 348-58 LID - S0022-4804(14)00257-1 [pii] LID - 10.1016/j.jss.2014.03.027 [doi] AB - BACKGROUND: Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) can lead to aortic wall failure. We hypothesized that patients with aneurysms resulting from chronic descending thoracic aortic dissection have elevated tissue and plasma levels of specific MMPs and decreased tissue levels of TIMPs. MATERIALS AND METHODS: Aortic tissue was obtained from 25 patients who required surgical repair of descending thoracic aortic aneurysm due to chronic aortic dissection and from 17 organ-donor controls without aortic disease. Tissue levels of MMP-1, -2, -3, -9, -12, and -13 and TIMP-1 and -2 were measured by colorimetric activity assay or enzyme-linked immunosorbent assay and confirmed by Western blot and immunohistochemistry. Blood obtained from the 25 patients and 15 controls without aortic diseases was used to compare plasma levels of MMP-3, -9, and -12. RESULTS: Total MMP-1, total MMP-9, and active MMP-9 levels were higher and total MMP-2 levels were lower in dissection tissue than in control tissue. Additionally, the MMP-9 to TIMP-1 and active to total MMP-2 ratios were higher and the MMP-2 to TIMP-2 ratio was lower in dissection tissue. Furthermore, patients had higher plasma active to total MMP-9 ratios than the controls. Age and hypertension were associated with increased MMP levels. CONCLUSIONS: Increased levels of several MMPs and increased MMP to TIMP ratios in aortic tissue from patients suggest an environment that favors proteolysis, which may promote progressive extracellular matrix destruction and medial degeneration after aortic dissection. An elevated active to total MMP-9 ratio in plasma may be a biomarker for end-stage aneurysm development in patients with chronic thoracic aortic disease. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Zhang, Xiaoming AU - Zhang X AD - Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas; Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong, China. FAU - Wu, Darrell AU - Wu D AD - Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas. FAU - Choi, Justin C AU - Choi JC AD - Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas. FAU - Minard, Charles G AU - Minard CG AD - Dan L. Duncan Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas. FAU - Hou, Xinguo AU - Hou X AD - Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas. FAU - Coselli, Joseph S AU - Coselli JS AD - Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas. FAU - Shen, Ying H AU - Shen YH AD - Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas. FAU - LeMaire, Scott A AU - LeMaire SA AD - Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas. Electronic address: slemaire@bcm.edu. LA - eng GR - K08 HL080085/HL/NHLBI NIH HHS/United States GR - M01 RR000188/RR/NCRR NIH HHS/United States GR - P50 HL083794/HL/NHLBI NIH HHS/United States GR - T32 HL007676/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140319 PL - United States TA - J Surg Res JT - The Journal of surgical research JID - 0376340 RN - 0 (Tissue Inhibitor of Metalloproteinases) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Aged MH - Aortic Dissection/blood/*enzymology MH - Aorta, Thoracic/*enzymology MH - Aortic Aneurysm/blood/*enzymology MH - Case-Control Studies MH - Chronic Disease MH - Female MH - Humans MH - Male MH - Matrix Metalloproteinases/*blood MH - Middle Aged MH - Tissue Inhibitor of Metalloproteinases/*blood PMC - PMC4065027 MID - NIHMS587388 OTO - NOTNLM OT - Aortic dissection OT - Matrix metalloproteinase OT - Tissue inhibitor of metalloproteinases EDAT- 2014/04/22 06:00 MHDA- 2014/08/08 06:00 PMCR- 2015/06/15 CRDT- 2014/04/22 06:00 PHST- 2013/12/04 00:00 [received] PHST- 2014/03/05 00:00 [revised] PHST- 2014/03/12 00:00 [accepted] PHST- 2014/04/22 06:00 [entrez] PHST- 2014/04/22 06:00 [pubmed] PHST- 2014/08/08 06:00 [medline] PHST- 2015/06/15 00:00 [pmc-release] AID - S0022-4804(14)00257-1 [pii] AID - 10.1016/j.jss.2014.03.027 [doi] PST - ppublish SO - J Surg Res. 2014 Jun 15;189(2):348-58. doi: 10.1016/j.jss.2014.03.027. Epub 2014 Mar 19.