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Citations to this article

Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model.
E Allaire, … , B Starcher, A W Clowes
E Allaire, … , B Starcher, A W Clowes
Published October 1, 1998
Citation Information: J Clin Invest. 1998;102(7):1413-1420. https://doi.org/10.1172/JCI2909.
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Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model.

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Abstract

Although matrix metalloproteinases (MMPs) are expressed in abundance in arterial aneurysms, their contribution to arterial wall degeneration, dilation, and rupture has not been determined. We investigated MMP function in a rat model of aneurysm associated with arterial dilation, elastin loss, medial invasion by mononuclear inflammatory cells, and MMP upregulation. Rupture was correlated with increased gelatinase B (MMP-9) and activated gelatinase A (MMP-2). Syngeneic rat smooth muscle cells retrovirally transfected with tissue inhibitor of matrix metalloproteinases (TIMP)-1 cDNA (LTSN) or with the vector alone as a control (LXSN) were seeded onto the luminal surface of the vessels. The seeding of LTSN cells resulted in TIMP-1 local overexpression. The seeding with LTSN cells, but not LXSN cells, decreased MMP-9, activated MMP-2 and 28-kD caseinase and elastase activity, preserved elastin in the media, and prevented aneurysmal degeneration and rupture. We conclude that MMP overexpression is responsible for aneurysmal degeneration and rupture in this rat model and that local pharmacological blockade might be a reasonable strategy for controlling the formation of aneurysms in humans.

Authors

E Allaire, R Forough, M Clowes, B Starcher, A W Clowes

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Proteinase Systems and Thoracic Aortic Aneurysm Progression
JR Barbour, FG Spinale, JS Ikonomidis
Journal of Surgical Research 2007
Efferent vagal nerve stimulation induces tissue inhibitor of metalloproteinase-1 in myocardial ischemia-reperfusion injury in rabbit
K Uemura, M Li, T Tsutsumi, T Yamazaki, T Kawada, A Kamiya, M Inagaki, K Sunagawa, M Sugimachi
American journal of physiology. Heart and circulatory physiology 2007
Essentials of Restenosis
HJ Duckers, EG Nabel, PW Serruys
2007
Effects of tissue inhibitor of metalloproteinase 2 deficiency on aneurysm formation
W Xiong, R Knispel, J Mactaggart, BT Baxter
Journal of Vascular Surgery 2006
Pharmacological targets in the treatment of abdominal aortic aneurysms
MP Bergoeing, RW Thompson, JA Curci
Expert Opinion on Therapeutic Targets 2006
Apolipoprotein E Knockout Mice Over-Expressing Human Tissue Inhibitor of Metalloproteinase 1 Are Protected against Aneurysm Formation but Not against Atherosclerotic Plaque Development
C Cuaz-Pérolin, I Jguirim, G Larigauderie, A Jlassi, C Furman, M Moreau, MJ Chapman, JC Fruchart, MN Slimane, H Mezdour, M Rouis
Journal of Vascular Research 2006
Increased serum cathepsin S in patients with atherosclerosis and diabetes
J Liu, L Ma, J Yang, A Ren, Z Sun, G Yan, J Sun, H Fu, W Xu, C Hu, GP Shi
Atherosclerosis 2006
Oral Administration of Diferuloylmethane (Curcumin) Suppresses Proinflammatory Cytokines and Destructive Connective Tissue Remodeling in Experimental Abdominal Aortic Aneurysms
F Parodi, D Mao, T Ennis, M Pagano, R Thompson
Annals of Vascular Surgery 2006
Targeting matrix metalloproteases to improve cutaneous wound healing
M Xue, NT Le, CJ Jackson
Expert Opinion on Therapeutic Targets 2006
Matrix metalloproteinases 2 and 9 in human atherosclerotic and non-atherosclerotic cerebral aneurysms
J Caird, C Napoli, C Taggart, M Farrell, D Bouchier-Hayes
European Journal of Neurology 2006
Percutaneous transplantation of genetically-modified autologous fibroblasts in the rabbit femoral artery: a novel approach for cardiovascular gene therapy
M Mazighi, D Tchétché, Y Gouëffic, AS Juan, L Louedec, D Hénin, JB Michel, MP Jacob, LJ Feldman
Journal of Vascular Surgery 2006
Matrix Metalloproteinase 2 Polymorphisms in a Caucasian Population with Abdominal Aortic Aneurysm
I Hinterseher, H Bergert, E Kuhlisch, A Bloomenthal, C Pilarsky, D Ockert, S Schellong, HD Saeger, D Krex
Journal of Surgical Research 2006
Vascular Medicine
ES Klings, J Loscalzo
Vascular Medicine 2006
Metaloproteinasas de matriz: su implicación en las enfermedades vasculares periféricas
JC Bohórquez-Sierra
Angiología 2006
Deficiencies in estrogen-mediated regulation of cerebrovascular homeostasis may contribute to an increased risk of cerebral aneurysm pathogenesis and rupture in menopausal and postmenopausal women
CG Harrod, HH Batjer, BR Bendok
Medical Hypotheses 2006
Pathobiology of Idiopathic Ascending Aortic Aneurysms
EW Kirsch, NC Radu, E Allaire, DY Loisance
Asian Cardiovascular and Thoracic Annals 2006
Principles of Molecular Medicine
MS Runge, C Patterson
2006
Increased Angiogenesis at the Site of Abdominal Aortic Aneurysm Rupture
E Choke, GW Cockerill, J Dawson, RW Wilson, A Jones, IM Loftus, MM Thompson
Annals of the New York Academy of Sciences 2006
Macrophage migration inhibitory factor induces MMP-9 expression: implications for destabilization of human atherosclerotic plaques
YZ Kong, X Yu, JJ Tang, X Ouyang, XR Huang, G Fingerle-Rowson, M Bacher, LA Scher, R Bucala, HY Lan
Atherosclerosis 2005
Enhancement of MMP-9 Activity in THP-1 Cells by 7-ketocholesterol and Its Suppression by the HMG-CoA Reductase Inhibitor Fluvastatin
H Ozaki, Y Miyashita, H Watanabe, K Shirai
Journal of Atherosclerosis and Thrombosis 2005
A Review of Biological Factors Implicated in Abdominal Aortic Aneurysm Rupture
E Choke, G Cockerill, WR Wilson, S Sayed, J Dawson, I Loftus, MM Thompson
European Journal of Vascular and Endovascular Surgery 2005
Gender Differences in Rat Aortic Smooth Muscle Cell Matrix Metalloproteinase-9
DT Woodrum, JW Ford, G Ailawadi, CG Pearce, I Sinha, MJ Eagleton, PK Henke, JC Stanley, GR Upchurch
Journal of the American College of Surgeons 2005
Up-Regulation and Coexpression of MIF and Matrix Metalloproteinases in Human Abdominal Aortic Aneurysms
L Verschuren, JH Lindeman, JH van Bockel, H Abdul-Hussien, T Kooistra, R Kleemann
Antioxidants & Redox Signaling 2005
Cell transplantation preserves matrix homeostasis: A novel paracrine mechanism
PW Fedak, PE Szmitko, RD Weisel, SM Altamentova, N Nili, N Ohno, S Verma, S Fazel, BH Strauss, RK Li
The Journal of Thoracic and Cardiovascular Surgery 2005
Regression of abdominal aortic aneurysm by inhibition of c-Jun N-terminal kinase
K Yoshimura, H Aoki, Y Ikeda, K Fujii, N Akiyama, A Furutani, Y Hoshii, N Tanaka, R Ricci, T Ishihara, K Esato, K Hamano, M Matsuzaki
Nature Medicine 2005
Suppression of experimental abdominal aortic aneurysms in mice by treatment with pyrrolidine dithiocarbamate, an antioxidant inhibitor of nuclear factor-κB
FE Parodi, D Mao, TL Ennis, MA Bartoli, RW Thompson
Journal of Vascular Surgery 2005
Enhanced abdominal aortic aneurysm in TIMP-1-deficient mice1
MK Eskandari, JD Vijungco, A Flores, J Borensztajn, V Shively, WH Pearce
Journal of Surgical Research 2005
Endovascular Treatment of Aneurysms: Gene Expression of Neointimal Cells Recruited on the Embolic Agent and Evolution with Recurrence in an Experimental Model
J Raymond, C Ogoudikpe, I Salazkin, A Metcalfe, G Gevry, M Chagnon, O Robledo
Journal of Vascular and Interventional Radiology 2005
An Overview of Matrix Metalloproteinases in the Pathogenesis and Treatment of Abdominal Aortic Aneurysms
WB Keeling, PA Armstrong, PA Stone, DF Bandyk, ML Shames
Vascular and endovascular surgery 2005
Dual Role of Matrix Metalloproteinases (Matrixins) in Intimal Thickening and Atherosclerotic Plaque Rupture
AC Newby
Physiological reviews 2005
Elevated levels of matrix metalloprotein-3 in patients with coronary aneurysm: A case control study
I Tengiz, E Ercan, E Aliyev, C Sekuri, C Duman, I Altuglu
Current controlled trials in cardiovascular medicine 2004
Vascular Smooth Muscle Cell Endovascular Therapy Stabilizes Already Developed Aneurysms in a Model of Aortic Injury Elicited by Inflammation and Proteolysis:
E Allaire, B Muscatelli-Groux, AM Guinault, C Pages, A Goussard, C Mandet, P Bruneval, D Mllire, JP Becquemin
Annals of Surgery 2004
Matrix metalloproteinases and atherosclerosis
N Watanabe, U Ikeda
Current Atherosclerosis Reports 2004
Optimization ofin vitro vascular cell transfection with non-viral vectors forin vivo applications
I Elmadbouh, P Rossignol, O Meilhac, R Vranckx, C Pichon, B Pouzet, P Midoux, JB Michel
The Journal of Gene Medicine 2004
Role of leukocyte elastase in preventing cellular re-colonization of the mural thrombus
V Fontaine, Z Touat, EM Mtairag, R Vranckx, L Louedec, X Houard, B Andreassian, U Sebbag, T Palombi, MP Jacob, O Meilhac, JB Michel
The American Journal of Pathology 2004
Matrix metalloproteinases: contribution to pathogenesis, diagnosis, surveillance and treatment of abdominal aortic aneurysms
NP Kadoglou, CD Liapis
Current Medical Research and Opinion 2004
Application of real-time RT-PCR to quantifying gene expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human abdominal aortic aneurysm
T Higashikata, M Yamagishi, H Sasaki, K Minatoya, H Ogino, H Ishibashi-Ueda, H Hao, N Nagaya, H Tomoike, A Sakamoto
Atherosclerosis 2004
Matrix metalloproteinase activity in thoracic aortic aneurysms associated with bicuspid and tricuspid aortic valves
J Boyum, EK Fellinger, JD Schmoker, L Trombley, K McPartland, FP Ittleman, AB Howard
The Journal of Thoracic and Cardiovascular Surgery 2004
Thérapie génique des resténoses et de l'athérosclérose : espoirs et réalités
M Mazighi, D Tchétché, F Hyafil, LJ Feldman
Pathologie Biologie 2004
Proteases and Their Inhibitors in Cancer Metastasis
JM Foidart, RJ Muschel
2004
Deficiency of Cathepsin S Reduces Atherosclerosis In Low-Density Lipoprotein Receptor-Deficient Mice
Galina K. Sukhova, Yaou Zhang, Jie-Hong Pan, Youichiro Wada, Takashi Yamamoto, Makoto Naito, Tatsuhiko Kodama, Sotirios Tsimikas, Joseph L. Witztum, Michael L. Lu, Yasuhiko Sakara, Michael T. Chin, Peter Libby, Guo-Ping Shi
Journal of Clinical Investigation 2003
Different expression of MMPs/TIMP-1 in human atherosclerotic lesions. Relation to plaque features and vascular bed
J Orbe, L Fernandez, JA Rodrıxguez, G Rábago, M Belzunce, A Monasterio, C Roncal, JA Páramo
Atherosclerosis 2003
Vascular smooth muscle cells efficiently activate a new proteinase cascade involving plasminogen and fibronectin
X Houard, C Monnot, V Dive, P Corvol, M Pagano
Journal of Cellular Biochemistry 2003
Mechanism of inhibition of matrix metalloproteinase-2 expression by doxycycline in human aortic smooth muscle cells
J Liu, W Xiong, L Baca-Regen, H Nagase, BT Baxter
Journal of Vascular Surgery 2003
Metalloproteinases in Development and Progression of Vascular Disease
HR Lijnen
Pathophysiology of Haemostasis and Thrombosis 2003
The dynamic extracellular matrix: intervention strategies during heart failure and atherosclerosis
S Heeneman, JP Cleutjens, BC Faber, EE Creemers, RJ Suylen, E Lutgens, KB Cleutjens, MJ Daemen
The Journal of Pathology 2003
Vascular matrix remodeling in patients with bicuspid aortic valve malformations: implications for aortic dilatation
PW Fedak, MP de Sa, S Verma, N Nili, P Kazemian, J Butany, BH Strauss, RD Weisel, TE David
The Journal of Thoracic and Cardiovascular Surgery 2003
Extracellular matrix remodeling and matrix metalloproteinases in the vascular wall during aging and in pathological conditions
MP Jacob
Biomedicine & Pharmacotherapy 2003
A murine model of thoracic aortic aneurysms
JS Ikonomidis, WC Gibson, J Gardner, S Sweterlitsch, RP Thompson, R Mukherjee, FG Spinale
Journal of Surgical Research 2003
Airway smooth muscle—its relationship to the extracellular matrix
JL Black, JK Burgess, PR Johnson
Respiratory Physiology & Neurobiology 2003
A nonintrinsic regional basis for increased infrarenal aortic MMP-9 expression and activity
G Ailawadi, BS Knipp, G Lu, KJ Roelofs, JW Forda, KK Hannawaa, K Bishop, P Thanaporna, PK Henke, JC Stanley, GR Upchurch
Journal of Vascular Surgery 2003
Paracrine secretion of transforming growth factor-β1 in aneurysm healing and stabilization with endovascular smooth muscle cell therapy1 1Competition of interest: none
F Losy, J Dai, C Pages, M Ginat, B Muscatelli-Groux, AM Guinault, E Rousselle, G Smedile, D Loisance, JP Becquemin, E Allaire
Journal of Vascular Surgery 2003
Prospects for the Medical Management of Abdominal Aortic Aneurysms
EF Steinmetz, C Buckley, RW Thompson
Vascular and endovascular surgery 2003
Increased Medial Degradation With Pseudo-Aneurysm Formation in Apolipoprotein E–Knockout Mice Deficient in Tissue Inhibitor of Metalloproteinases-1
V Lemaître, PD Soloway, J DArmiento
Circulation 2003
Matrix metalloproteinase 2 and 9 work in concert to produce aortic aneurysms
G. Matthew Longo, Wanfen Xiong, Timothy C. Greiner, Yong Zhao, Nicola Fiotti, B. Timothy Baxter
Journal of Clinical Investigation 2002
Systemic tissue inhibitor of metalloproteinase-1 gene delivery reduces neointimal hyperplasia in balloon-injured rat carotid artery
C Furman, Z Luo, K Walsh, N Duverger, C Copin, JC Fruchart, M Rouis
FEBS Letters 2002
Involvement of the mural thrombus as a site of protease release and activation in human aortic aneurysms
V Fontaine, MP Jacob, X Houard, P Rossignol, D Plissonnier, E Angles-Cano, JB Michel
The American Journal of Pathology 2002
Mechanisms of abdominal aortic aneurysm formation
A Daugherty, LA Cassis
Current Atherosclerosis Reports 2002
Matrix metalloproteinases and atherosclerotic plaque instability
IM Loftus, AR Naylor, PR Bell, MM Thompson
The British journal of surgery 2002
Therapeutic developments in matrix metalloproteinase inhibition
PK Shah, DJ Wilkin, TM Doherty, H Uzui, TB Rajavashisth, K Asotra, D Pei
Expert Opinion on Therapeutic Patents 2002
Polymorphisms in the promoter regions of MMP-2, MMP-3, MMP-9 and MMP-12 genes as determinants of aneurysmal coronary artery disease
N Lamblin, C Bauters, X Hermant, JM Lablanche, N Helbecque, P Amouyel
Journal of the American College of Cardiology 2002
Differential regulation of matrix metalloproteinase activities in abdominal aortic aneurysms
B Annabi, D Shédid, P Ghosn, RL Kenigsberg, RR Desrosiers, MW Bojanowski, E Beaulieu, E Nassif, R Moumdjian, R Béliveau
Journal of Vascular Surgery 2002
Genes potentially involved in plaque rupture
BC Faber, S Heeneman, MJ Daemen, KB Cleutjens
Current Opinion in Lipidology 2002
Proteolysis of the Abdominal Aortic Aneurysm Wall and the Association with Rupture
E Petersen, F Wågberg, KA Ängquist
European Journal of Vascular and Endovascular Surgery 2002
Abdominal Aortic Aneurysms: Basic Mechanisms and Clinical Implications
RW Thompson, PJ Geraghty, JK Lee
Current Problems in Surgery 2002
The role of matrix metalloproteinases in vascular disease
IM Loftus, MM Thompson
Vascular medicine (London, England) 2002
Metalloproteinase Inhibition and the Response to Angioplasty and Stenting in Atherosclerotic Primates
GS Cherr, SJ Motew, JA Travis, J Fingerle, L Fisher, M Brandl, JK Williams, RL Geary
Arteriosclerosis, thrombosis, and vascular biology 2002
Matrix Metalloproteinases in Vascular Remodeling and Atherogenesis: The Good, the Bad, and the Ugly
ZS Galis, JJ Khatri
Circulation research 2002
Matrix Metalloproteinases: Are They Antiatherogenic but Proaneurysmal?
MP Bendeck
Circulation research 2002
Oxidative Stress in Human Abdominal Aortic Aneurysms: A Potential Mediator of Aneurysmal Remodeling
FJ Miller, WJ Sharp, X Fang, LW Oberley, TD Oberley, NL Weintraub
Arteriosclerosis, thrombosis, and vascular biology 2002
Reduced Atherosclerotic Plaque but Enhanced Aneurysm Formation in Mice With Inactivation of the Tissue Inhibitor of Metalloproteinase-1 ( TIMP-1 ) Gene
J Silence, D Collen, HR Lijnen
Circulation research 2002
Cellular Peptidases in Immune Functions and Diseases 2
J Langner, S Ansorge
2002
Phenotypic alteration of vascular smooth muscle cells precedes elastolysis in a mouse model of Marfan syndrome
TE Bunton, NJ Biery, L Myers, B Gayraud, F Ramirez, HC Dietz
Circulation research 2001
Endoluminal smooth muscle cell seeding limits intimal hyperplasia
D Gomes, L Louedec, D Plissonnier, MC Dauge, D Henin, M Osborne-Pellegrin, JB Michel
Journal of Vascular Surgery 2001
Genetic Studies on the Role of Proteinases and Growth Factors in Atherosclerosis and Aneurysm Formation
A Luttun, P Carmeliet
Annals of the New York Academy of Sciences 2001
Surgical Research
J Rozga, AA Demetriou
Surgical Research 2001
MMP9 production by human monocyte-derived macrophages is decreased on polymerized type I collagen
S Lepidi, RD Kenagy, EW Raines, ES Chiu, A Chait, R Ross, AW Clowes
Journal of Vascular Surgery 2001
The expression and localization of membrane type-1 matrix metalloproteinase in human abdominal aortic aneurysms
A Nollendorfs, TC Greiner, H Nagase, BT Baxter
Journal of Vascular Surgery 2001
Extracellular matrix remodeling in the vascular wall
MP Jacob, C Badier-Commander, V Fontaine, Y Benazzoug, L Feldman, JB Michel
Pathologie Biologie 2001
Elastin–laminin receptor and abdominal aortic aneurysms. New subject to study? A review
M Kunecki, A Nawrocka
Pathologie Biologie 2001
Compensatory Enlargement and Stenosis Develop in ApoE −/− and ApoE*3-Leiden Transgenic Mice
E Lutgens, ED de Muinck, S Heeneman, MJ Daemen
Arteriosclerosis, thrombosis, and vascular biology 2001
Contrasting Outcomes of Atheroma Evolution: Intimal Accumulation Versus Medial Destruction
JB Michel
Arteriosclerosis, thrombosis, and vascular biology 2001
Persistence of Atherosclerotic Plaque but Reduced Aneurysm Formation in Mice With Stromelysin-1 (MMP-3) Gene Inactivation
J Silence, F Lupu, D Collen, HR Lijnen
Arteriosclerosis, thrombosis, and vascular biology 2001
Differential Expression of Matrix Metalloproteinases After Stent Implantation and Balloon Angioplasty in the Hypercholesterolemic Rabbit
LJ Feldman, M Mazighi, A Scheuble, JF Deux, ED Benedetti, C Badier-Commander, E Brambilla, D Henin, PG Steg, MP Jacob
Circulation 2001
Polymorphisms in Matrix Metalloproteinase-1, -3, -9, and -12 Genes in Relation to Subarachnoid Hemorrhage
B Zhang, S Dhillon, I Geary, WM Howell, F Iannotti, IN Day, S Ye
Stroke; a journal of cerebral circulation 2001
The role of proteinases in angiogenesis, heart development, restenosis, atherosclerosis, myocardial ischemia, and stroke: Insights from genetic studies
A Luttun, M Dewerchin, D Collen, P Carmeliet
Current Atherosclerosis Reports 2000
Proteinases in cardiovascular aneurysms and rupture: targets for therapy?
P Carmeliet
Journal of Clinical Investigation 2000
Angiotensin II, atherosclerosis, and aortic aneurysms
BC Berk, J Haendeler, J Sottile
Journal of Clinical Investigation 2000
Preoperative treatment with doxycycline reduces aortic wall expression and activation of matrix metalloproteinases in patients with abdominal aortic aneurysms
JA Curci, D Mao, DG Bohner, BT Allen, BG Rubin, JM Reilly, GA Sicard, RW Thompson
Journal of Vascular Surgery 2000
Cardiovascular gene therapy
S Ylä-Herttuala, JF Martin
The Lancet 2000
PROSPECTS FOR GENETIC THERAPY OF CARDIOVASCULAR DISEASE
HJ Duckers, EG Nabel
Medical Clinics of North America 2000
Molecular interactions between the plasminogen/plasmin and matrix metalloproteinase systems
HR Lijnen
Fibrinolysis and Proteolysis 2000
Prospectives pour une biologie cellulaire chirurgicale
JB Michel
Annales de Chirurgie 2000
Plasminogen activators, matrix metalloproteinases and their inhibitors in implanted vascular prostheses
H Urayama, S Katada, F Kasashima, Y Tanaka, K Kawasuji, Y Watanabe
European Journal of Vascular and Endovascular Surgery 2000
Circulating Biochemical Marker Levels of Collagen Metabolism Are Abnormal in Patients with Abdominal Aortic Aneurysm
R Tachieda, H Niinuma, A Ohira, S Endoh, K Hiramori, S Makita, M Nakamura
Angiology 2000
Metalloproteinase Inhibition Reduces Constrictive Arterial Remodeling After Balloon Angioplasty: A Study in the Atherosclerotic Yucatan Micropig
BJ de Smet, D de Kleijn, R Hanemaaijer, JH Verheijen, L Robertus, YJ van der Helm, C Borst, MJ Post
Circulation 2000
Cystatin C deficiency in human atherosclerosis and aortic aneurysms
GP Shi, GK Sukhova, A Grubb, A Ducharme, LH Rhode, RT Lee, PM Ridker, P Libby, HA Chapman
Journal of Clinical Investigation 1999
Who are the proteolytic culprits in vascular disease?
WC Parks
Journal of Clinical Investigation 1999
Marimastat inhibits elastin degradation and matrix metalloproteinase 2 activity in a model of aneurysm disease
GD Treharne, JR Boyle, S Goodall, IM Loftus, PR Bell, MM Thompson
The British journal of surgery 1999
Tissue Inhibitor of Matrix Metalloproteinases-1 Impairs Arterial Neointima Formation After Vascular Injury in Mice
HR Lijnen, P Soloway, D Collen
Circulation research 1999
Abdominal aortic aneurysm
JA van der Vliet, AP Boll
The Lancet 1997

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