Buscar en
Angiología
Toda la web
Inicio Angiología Metaloproteinasas de matriz: su implicación en las enfermedades vasculares peri...
Información de la revista
Vol. 58. Núm. 4.
Páginas 269-277 (Enero 2006)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 58. Núm. 4.
Páginas 269-277 (Enero 2006)
DOI: 10.1016/S0003-3170(06)74981-1
Acceso a texto completo
Metaloproteinasas de matriz: su implicación en las enfermedades vasculares periféricas
Matrix metalloproteases: their involvement in peripheral vascular diseases
Visitas
...
J.C. Bohórquez-Sierra
Autor para correspondencia
jcbsierra@terra.es

Correspondencia: Unidad de Angiología y Cirugía Vascular. Hospital Universitario Puerta del Mar. Avda. Ana de Viya, 21. E-11009 Cádiz. Fax: +34 956 002491.
Unidad de Angiología y Cirugía Vascular. Hospital Universitario Puerta del Mar. Cádiz, España
Información del artículo
Resumen
Bibliografía
Descargar PDF
Estadísticas
Resumen
Objetivos

Aportar los conceptos básicos sobre la estructura y la función de las metaloproteinasas de matriz (MMP) y exponer de forma resumida la información bibliográfica actualizada sobre su implicación en las enfermedades vasculares periféricas.

Desarrollo

La matriz extracelular desempeña un papel esencial en el mantenimiento de la integridad del sistema cardiovascular. En condiciones normales, las fibras de elastina y colágeno resisten la desestructuración espontánea y pueden degradarse por las MMP. Las MMP son enzimas proteolíticas que se encargan de la remodelación de la matriz extracelular y, en su conjunto, pueden degradar todos los constituyentes de ésta. Diversas publicaciones han demostrado la implicación de las MMP en algunas vasculopatías, especialmente en la formación de aneurismas, la hiperplasia intimal, la ateroesclerosis y las úlceras venosas, lo que ha llevado a estudiar la inhibición de las MMP en modelos experimentales de enfermedades vasculares.

Conclusiones

Las MMP, por su capacidad de degradar los componentes de la matriz extracelular, son enzimas que desempeñan un papel importante en procesos biológicos y patológicos múltiples, entre ellos algunas enfermedades vasculares. Los avances en el conocimiento de sus mecanismos de activación, la especificidad de sustratos y los mecanismos de inhibición por los inhibidores tisulares de las MMP han permitido el diseño de inhibidores sintéticos de las metaloproteinasas que probablemente permitan diseñar en el futuro nuevas estrategias terapéuticas para combatir dichas enfermedades.

Palabras clave:
Aneurisma
Ateroesclerosis
Hiperplasia intimal
Inhibidores tisulares de las metaloproteinasas
Insuficiencia venosa crónica
Metaloproteinasa
Summary
Aims

To report on the fundamental concepts concerning the structure and function of metalloproteases and to offer a brief summary of the latest data from the literature about the involvement of matrix metalloproteases (MMPs) in peripheral vascular diseases.

Development

The extracellular matrix plays an essential role in maintaining the integrity of the cardiovascular system. Under normal conditions, elastin and collagen fibres withstand spontaneous destructuring and can be degraded by MMPs. MMPs are proteolytic enzymes that are responsible for remodelling the extracellular matrix and, taken as a whole, can degrade all its components. Several publications have demonstrated the involvement of MMPs in certain vascular diseases, especially in the formation of aneurysms, intimal hyperplasias, atherosclerosis and venous ulcers, and this has led researchers to study the inhibition of MMPs in experimental models of vascular diseases.

Conclusions

Owing to their capacity to degrade the components of the extracellular matrix, MMPs are enzymes that play an important role in numerous biological and pathological processes, including some vascular diseases. The progress being made in our understanding of its mechanisms of action, substrate specificity and the mechanisms of inhibition used by the tissue inhibitors of MMPs has enabled us to design synthetic metalloprotease inhibitors that will probably make it possible in the future to design new therapeutic strategies with which to fight these diseases.

Key words:
Aneurysm
Atherosclerosis
Chronic venous insufficiency
Intimal hyperplasia
Metalloprotease
Tissue inhibitors of metalloproteases
El Texto completo está disponible en PDF
Bibliografía
[1.]
Shapiro S.D..
Matrix metalloproteinase degradation of extracellular matrix: biological consequences.
Curr Opin Cell Biol, 10 (1998), pp. 602-608
[2.]
McDonnell S., Morgan M., Lynch C..
Role of matrix metalloproteinases in normal and disease processes.
Biochem Soc Trans, 27 (1999), pp. 734-740
[3.]
Nagase H., Woessner J.F. Jr.
Matrix metalloproteinases.
J Biol Chem, 274 (1999), pp. 21491-21494
[4.]
Sternlicht M.D., Werb Z..
How matrix metalloproteinases regulate cell behavior.
Annu Rev Cell Dev Biol, 17 (2001), pp. 463-516
[5.]
Mazzieri R., Masiero L., Zanetta L., Monea S., Onisto M., Garbisa S., et al.
Control of type IV collagenase activity by components of the urokinase-plasmin system: a regulatory mechanism with cell-bound reactants.
EMBO J, 16 (1997), pp. 2319-2332
[6.]
Estreicher A., Muhlhauser J., Carpentier J.L., Orci L., Vassalli J.D..
The receptor for urokinase type plasminogen activator polarizes expression of the protease to the leading edge of migrating monocytes and promotes degradation of enzyme inhibitor complexes.
J Cell Biol, 111 (1990), pp. 783-792
[7.]
Loftus I.M., Thompson M.M..
The role of matrix metalloproteinases in vascular disease.
Vasc Med, 7 (2002), pp. 117-133
[8.]
Baker A.H., Zaltsman A.B., George S.J., Newby A.C..
Divergent effects of tissue inhibitor of metalloproteinase-1, -2 or -3 overexpression on rat vascular smooth muscle cell invasion, proliferation and death, in vitro.
J Clin Invest, 101 (1998), pp. 1478-1487
[9.]
Pauly R.R., Passaniti A., Bilato C., Monticone R., Cheng L., Papadopoulos N., et al.
Migration of cultured vascular smooth muscle cells through a basement membrane barrier requires type IV collagenase activity and is inhibited by cellular differentiation.
Circ Res, 75 (1994), pp. 41-54
[10.]
Galis Z.S., Sukhova G.K., Lark M.W., Libby P..
Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques.
J Clin Invest, 94 (1994), pp. 2493-2503
[11.]
Shonbeck U., Mach F., Sukhova G.K., Murphy C., Bonnefoy J.Y., Fabunmi R.P., et al.
Regulation of matrix metalloproteinase expression in human vascular smooth cells by T lymphocytes: a role for CD40 signaling in plaque rupture?.
Circ Res, 81 (1997), pp. 448-454
[12.]
Vine N., Powell J.T..
Metalloproteinases in degenerative aortic disease.
Clin Sci, 81 (1991), pp. 233-239
[13.]
Loftus I.M., Naylor A.R., Goodall S., Crowther M., Jones L., Bell P.R., et al.
Increased matrix metalloproteinase-9 activity in unstable carotid plaques. A potential role in acute plaque disruption.
Stroke, 31 (2000), pp. 40-47
[14.]
Nikkari S.T., O'Brien K.D., Ferguson M., Hatsukami T., Welgus H.G., Alpers C.E., et al.
Interstitial collagenase (MMP-1) expression in human carotid atherosclerosis.
Circulation, 92 (1995), pp. 1393-1398
[15.]
Halpert I., Sires U.I., Roby J.D., Potter-Perigo S., Wight T.N., Shapiro S.D., et al.
Matrilysin is expressed by lipid-laden macrophages at sites of potential rupture in atherosclerotic lesions and localises to areas of versican deposition, a proteoglycan substrate for the enzyme.
Proc Natl Acad Sci U S A, 93 (1996), pp. 9748-9753
[16.]
Fukumoto Y., Libby P., Rabkin E., Hill C.C., Enomoto M., Hirouchi Y., et al.
Statins alter smooth muscle cell accumulation and collagen content in established atheroma of watanabe heritable hyperlipidemic rabbits.
Circulation, 103 (2001), pp. 276-283
[17.]
Crisby M., Nordin-Fredriksson G., Shah P.K., Yano J., Zhu J., Nilsson J..
Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization.
Circulation, 103 (2001), pp. 926-933
[18.]
Dobrin P.B., Mrkvicka R..
Failure of elastin or collagen as possible critical connective tissue alterations underlying aneurysmal dilatation.
Cardiovasc Surg, 2 (1994), pp. 484-488
[19.]
Halloran B.G., Baxter B.T..
Pathogenesis of aneurysms.
Semin Vasc Surg, 8 (1995), pp. 85-92
[20.]
White J.V., Haas K., Phillips S., Comerota A.J..
Adventitial elastolysis is a primary event in aneurysmal development.
J Vasc Surg, 17 (1993), pp. 371-380
[21.]
Tamarina N.A., McMillan W.D., Shively V.P., Perce W.H..
Expression of matrix metalloproteinases and their inhibitors in aneurysms and normal aorta.
Surgery, 122 (1997), pp. 264-271
[22.]
Knox J.B., Sukhova G.K., Whittemore A.D., Libby P..
Evidence for altered balance between matrix metalloproteinases and their inhibitors in human aortic diseases.
Circulation, 95 (1997), pp. 205-212
[23.]
Patel M.I., Melrose J., Ghosh P., Appleberg M..
Increased synthesis of matrix metalloproteinases by aortic smooth muscle cells is implicated in the etiopathogenesis of abdominal aortic aneurysms.
J Vasc Surg, 24 (1996), pp. 82-92
[24.]
Crowther M., Brindle N.J., Sayers R., Bell P.F., Thompson M.M..
Aneurysmal smooth muscle cells exhibit increased matrix metalloproteinase-2 production in vitro.
Ann N Y Acad Sci, 800 (1996), pp. 283-285
[25.]
Davis V., Persidskaia R., Baca-Regen L., Itoh Y., Nagase H., Persidsky Y., et al.
Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms.
Arterioscler Thromb Vasc Biol, 18 (1998), pp. 1625-1633
[26.]
Curci J.A., Liao S., Huffman M.D., Shapiro S.D., Thompson R.W..
Expression and localization of macrophage elastase (matrix metalloproteinase-12) in abdominal aortic aneurysms.
J Clin Invest, 102 (1998), pp. 1900-1910
[27.]
Pyo R., Lee J.K., Shipley J.M., Curci J.A., Mao D., Ziporin S.J., et al.
Targeted gene disruption of MMP-9 (gelatinase B) suppreses development of experimental abdominal aortic aneurysms.
J Clin Invest, 105 (2001), pp. 1641-1649
[28.]
Carmeliet P..
Proteinases in cardiovascular aneurysms and rupture: targets for therapy?.
J Clin Invest, 105 (2000), pp. 1519-1520
[29.]
Davis M.G., Hagen P.O..
Pathobiology of intimal hyperplasia.
Br J Surg, 81 (1994), pp. 1254-1269
[30.]
Johnson J.L., Van Eys G.J.J.M., Angelini G.D., George S.J..
Injury induces dedifferentiation of smooth muscle cells and increased matrix-degrading metalloproteinase activity in human saphenous vein.
Arterioscler Thromb Vasc Biol, 21 (2001), pp. 1146-1151
[31.]
Southgate K.M., Fisher M., Banning A.P., Thurston V.J., Baker A.H., Fabunmi R.P., et al.
Upregulation of basement membrane-degrading metalloproteinase secretion after balloon injury of pig carotid arteries.
Circ Res, 79 (1996), pp. 1177-1187
[32.]
Lijnen H.R., Collen S.D..
Tissue inhibitor of matrix metalloproteinase-1 impairs arterial neointima formation after vascular injury in mice.
Circ Res, 85 (1999), pp. 1186-1191
[33.]
George S.J., Johnson J.L., Angellini A., Newby A.C., Baker A.H..
Adenovirus-mediated gene transfer of the human TIMP-1 gene inhibits smooth muscle cell migration and neointimal formation in human saphenous vein.
Hum Gene Ther, 9 (1998), pp. 867-877
[34.]
Weckroth M., Vaheri A., Lauharanta J., Sorsa T., Konttinen Y.T..
Matrix metalloproteinases, gelatinase and collagenase in chronic leg ulcers.
J Invest Dermatol, 106 (1996), pp. 1119-1124
[35.]
Saarialho-Kere U.K., Kovacs S.O., Pentland A.P., Olerud J.E., Welgus H.G., Parks W.C..
Cell-matrix interactions modulate interstitial collagenase expression by human keratinocytes actively involved in wound healing.
J Clin Invest, 92 (1993), pp. 2858-2866
[36.]
Vaalamo M., Leivo T., Saarialho-Kere U.K..
Differential expression of tissue inhibitors of metalloproteinases (TIMP-1, -2, -3 and -4) in normal and aberrant wound healing.
Hum Pathol, 30 (1999), pp. 795-802
[37.]
Allaire E., Forough R., Clowes M., Starcher B., Clowes A.W..
Local overexpression of TIMP-1 prevents aorticaneurysm degeneration and rupture in a rat model.
J Clin Invest, 102 (1998), pp. 1413-1420
[38.]
Rouis M., Adamy C., Duverger N., Lesnik P., Horellou P., Moreau M., et al.
Adenovirus-mediated overexpression of tissue inhibitor of metalloproteinase-1 reduces atherosclerotic lesions in apolipoprotein E-deficient mice.
Circulation, 100 (1999), pp. 533-540
[39.]
Bigatel D.A., Elmore J.R., Carey D.J., Cizmeci-Smith G., Franklin D.P., Youkey J.R..
The matrix metalloproteinase inhibitor BB-94 limits expansion of experimental abdominal aortic aneurysms.
J Vasc Surg, 29 (1999), pp. 130-139
[40.]
Porter K.E., Loftus I.M., Peterson M., Bell P.R., London N.J., Thompson M.M..
Marimastat inhibits neointimal thickening in a model of human vein graft stenosis.
Br J Surg, 85 (1998), pp. 1373-1377
[41.]
Treharne G.D., Boyle J.R., Goodal S., Loftus I.M., Bell P.R., Thompson M.M..
Marimastat inhibits elastin degradation and matrix metalloproteinase-2 activity in a model of aneurysm disease.
Br J Surg, 86 (1999), pp. 1053-1058
[42.]
Michaelides M.R., Curtin M.L..
Recent advances in matrix metalloproteinase inhibitors research.
Curr Pharm Des, 5 (1999), pp. 787-819
[43.]
Loftus I.M., Porter K., Peterson M., Boyle J., London N.M., Bell P.R., et al.
MMP inhibition reduces intimal hyperplasia in a human vein graft stenosis model.
Ann N Y Acad Sci, 878 (1999), pp. 547-550
[44.]
Petrinec D., Liao S., Holmes D.R., Reilly J.M., Parks W.C., Thompson R.W..
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.
J Vasc Surg, 23 (1996), pp. 336-346
[45.]
Thompson R.W., Baxter B.T..
MMP inhibition in abdominal aortic aneurysms: rationale for a prospective randomized clinical trial.
Ann N Y Acad Sci, 878 (1999), pp. 159-178
Copyright © 2006. SEACV
Opciones de artículo
Herramientas
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos

es en pt
Política de cookies Cookies policy Política de cookies
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.