Publique en esta revista
Información de la revista
Vol. 6. Núm. A.
Actualización y futuro del óxido nítrico en el tratamiento de la enfermedad cardiovascular
Páginas 21A-30A (Marzo 2006)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 6. Núm. A.
Actualización y futuro del óxido nítrico en el tratamiento de la enfermedad cardiovascular
Páginas 21A-30A (Marzo 2006)
Actualización y futuro del óxido nítrico en el tratamiento de la enfermedad cardiovascular
Acceso a texto completo
Disfunción endotelial
Endothelial Dysfunction
Visitas
...
Lina Badimón??
Autor para correspondencia
lbadimon@csic-iccc.santpau.es

Correspondencia: Dra. L. Badimón. Centro de Investigación Cardiovascular. Hospital de la Santa Creu i Sant Pau. Avda. San Antoni M. Claret, 167. 08025 Barcelona. España.
, José Martínez-González
Centro de Investigación Cardiovascular, CSIC-ICCC. Hospital de la Santa Creu y Sant Pau. Barcelona. España
Información del artículo
Resumen
Bibliografía
Descargar PDF
Estadísticas

La definición de nuevos abordajes para la prevención y el tratamiento de la arteriosclerosis y sus syndromes asociados es un alta necesidad y prioridad debido al impacto en la morbimortalidad y la salud pública de estas enfermedades. Recientemente, se ha demostrado que la evaluación de la disfunción endotelial, en su vertiente de vasorreactividad, es una herramienta de utilidad para valorar la arteriosclerosis. Los factores de riesgos clásicos y emergentes están demostrando su asociación con la disfunción endotelial y la clínica en la enfermedad cardiovascular se relaciona, en parte, con la pérdida de una función endotelial reguladora de la homeostasis vascular. En estudios recientes se indica que la severidad de la disfunción endotelial se asocia con el riesgo cardiovascular, y finalmente, muchas intervenciones farmacológicas y dietéticas que reducen el riesgo cardiovascular han demostrado mejorar la función endotelial. El endotelio y su función han entrado plenamente en la práctica clínica y el control de la función endotelial está emergiendo como la llave de terapias que pueden interferir en el desarrollo de la arteriosclerosis y sus complicaciones clínicas.

Palabras clave:
Endotelio
Cardiovascular
Aterosclerosis
Óxido nítrico
Abreviaturas:
ADMA
ADP
bFGF
CAM
CE
CML
eNOS
GMP
HDL
HMG-CoA
ICAM-I
IL
LDL
LDLox
MCP-1
NF-κβ
NO
NOS
PAF
PAI-I
PDGF
PECAM 1
PGI2
PPARγ
SREBP
SSRE
TNFα
t-PA
TXA2
VCAM
VLDL
vWF

The development of new approaches to the prevention and treatment of atherosclerosis and its clinical manifestations is a priority because of the impact these diseases have on morbidity, mortality and public health. Recently, it has been demonstrated that assessment of endothelial dysfunction can be useful in the evaluation of vascular disease. Both classical and newly identified risk factors have been shown to be associated with endothelial dysfunction. Indeed, loss of the endothelium's homeostatic regulatory function has been linked to the clinical manifestation of cardiovascular disease. Moreover, recent reports indicate that there is a correlation between the severity of endothelial dysfunction and cardiovascular risk. Finally, both dietary and pharmacological interventions aimed at reducing cardiovascular risk have been shown to improve endothelial function. Consequently, the endothelium and its function have now become important in clinical practice and the control of endothelial function is emerging as a key element of therapies designed to prevent the development of atherosclerosis and its clinical complications.

Key words:
Endothelium
Cardiovascular disease
Atherosclerosis
Nitric oxide
El Texto completo está disponible en PDF
Bibliografía
[1.]
Badimon L, Martínez-González J, Llorente-Cortés V, Rodríguez C, Padro T. Cell biology and lipoproteins in atherosclerosis. Curr Mol Med. En prensa.
[2.]
L. Badimon, J.J. Badimon, W. Penny, M.W. Webster, J.H. Chesebro, V. Fuster.
Endothelium and atherosclerosis.
J Hypertens, 10 (1992), pp. S43-S50
[3.]
L. Badimon, J. Martínez-González.
Endotelio en la protección vascular: nuevos conocimientos.
Rev Esp Cardiol, 55 (2002), pp. S17-S26
[4.]
L. Badimon.
Estatinas y función endotelial.
Rev Esp Cardiol, 3 (2003), pp. C25-40
[5.]
E. Dejana.
Cell adhesion in vascular biology.
J Clin Invest, 9 (1996), pp. 1949-1953
[6.]
B. Nordestgaard, L. Nielsen.
Atherosclerosis and arterial influx of lipoproteins.
Curr Opin Lipidol, 5 (1994), pp. 252-257
[7.]
B. Zhao, W.D. Ehringer, R. Dierichs, F.N. Miller.
Oxidized low-density lipoprotein increases endothelial intracellular calcium and alters cytoskeletal f-actin distribution.
Eur J Clin Invest, 27 (1997), pp. 48-54
[8.]
M. Essler, M. Retzer, M. Bauer, J.W. Heemskerk, M. Aepfelbacher, W. Siess.
Midly oxidized low density lipoprotein induces contraction of human endothelial cells through activation of Rho/Rho kinase and inhibition of myosin light chain phosphatase.
J Biol Chem, 274 (1999), pp. 30361-30364
[9.]
S. Pillarisetti.
Lipoprotein modulation of subendothelial heparin sulfate proteoglycans (Perlecan) and atherogenicity.
Trends Cardiovasc Med, 10 (2000), pp. 60-65
[10.]
C. Rodríguez, B. Raposo, J. Martínez-González, L. Casaní, L. Badimon.
Low density lipoproteins downregulate lysyl oxidase in vascular endothelial cells and in the arterial wall.
Arterioscler Thromb Vasc Biol, 22 (2002), pp. 1409-1414
[11.]
Badimón L, Martínez-González J. Bases moleculares y genéticas de las cardiopatías. En: Bayés de Luna A, López Sendon JL, Attie F, Alegría Ezquerra E, editores. Cardiología clínica. Barcelona: Editorial Masson, S.A.;22003.p.30-44.
[12.]
M.I. Cybulski, M.A. Gimbrone Jr.
Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis.
Science, 251 (1991), pp. 788-791
[13.]
D.M. Smalley, J.H.C. Lin, M.L. Curtis, Y. Kobari, M.B. Stemerman, K.A. Prichard.
Native LDL increases endothelial cell adhesiveness by inducing intercellular adhesion molecule-1.
Arterioscler Thromb Vasc Biol, 16 (1996), pp. 585-590
[14.]
B.V. Khan, S.S. Parthasarathy, R.W. Alexander, R.M. Medford.
Modified low density lipoprotein and its constituents augments cytokine-activated vascular cell adhesion molecule-1 gene expression in human vascular endothelial cells.
J Clin Invest, 95 (1995), pp. 1262-1270
[15.]
C. Colomé, J. Martínez-González, F. Vidal, C. De Castellarnau, L. Badimon.
Small oxidative changes in atherogenic LDL concentrations irreversibly regulate adhesiveness of human endothelial cells: effect of the lazaroid U74500A.
Atherosclerosis, 149 (2000), pp. 295-302
[16.]
R.R. Johson-Tidey, J.L. McGregor, P.R. Taylor, R.N. Poston.
Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. coexpression with intercellular adhesion molecule-1.
Am J Pathol, 144 (1994), pp. 952-961
[17.]
H. Ikeda, Y. Takajo, K. Ichiki, T. Ueno, S. Maki, T. Noda, et al.
Increased soluble form of P-selectin in patients with unstable angina.
Circulation, 92 (1995), pp. 1693-1696
[18.]
S.J. Hwang, C.M. Ballantyne, A.R. Sharret, L.C. Smith, C.E. Davis, A.M. Gotto, et al.
Circulating adhesion molecules VCAM-1, ICAM-1 and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the Atherosclerosis Risk In Communities (ARIC) study.
Circulation, 96 (1997), pp. 4219-4225
[19.]
Y. Abe, B. El-Masi, K.T. Kimball, H. Pownall, C.F. Reilly, K. Osmundsen, et al.
Soluble cell adhesion molecules in hypertriglyceridemia and potential significance on monocyte adhesion.
Arterioscler Thromb Vasc Biol, 18 (1998), pp. 723-731
[20.]
C.J.M. Frijns, L.J. Kappelle, J. Van Gijn, H.K. Nieuwenhuis, J.J. Sixma, R. Fijnheer.
Soluble adhesion molecules reflect endothelial cell activation in ischemic stroke and in carotid atherosclerosis.
Stroke, 28 (1997), pp. 2214-2218
[21.]
K. Peter, P. Nawroth, C. Conradt, T. Nordt, T. Weiss, M. Boehme, et al.
Circulating vascular cell adhesion molecule-1 correlates with the extent of human atherosclerosis in contrast to circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and trombomodulin.
Arterioscler Thromb Vasc Biol, 17 (1997), pp. 503-512
[22.]
P. Ridker, C. Hennekens, B. Roitman-Johson, M. Stampfer, J. Allen.
Plasma concentration of soluble intercellular adhesion molecule 1 and risk of future myocardial infarction in apparently healthy men.
[23.]
R. Alonso, P. Mata, R. De Andrés, B.P. Villacastin, J. Martínez-González, L. Badimon.
Sustained long-term improvement of arterial endothelial function in heterozygous familial hypercholesterolemia patients treated with simvastatin.
Atherosclerosis, 157 (2001), pp. 423-429
[24.]
A.M. Zeiher, H. Drexler, H. Wollschlager, H. Just.
Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis.
Circulation, 83 (1991), pp. 391-401
[25.]
P.R. Casino, M.K. Crescence, A.A. Quyyumi, J.M. Hoeg, J.A. Panza.
The role of nitric oxide in endothelium-dependent vasodilation of hypercholesterolemic patients.
Circulation, 88 (1993), pp. 2541-2547
[26.]
G. O’Driscoll, D. Green, R.R. Taylor.
Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month.
Circulation, 95 (1997), pp. 1126-1131
[27.]
S. John, M. Schlaich, M. Langenfeld, H. Weihprecht, G. Schmitz, G. Weidinger, et al.
Increased bioavailability of nitric oxide after lipid-lowering therapy in hypercholesterolemic patients. A randomized, placebo-controlled, double-blind study.
Circulation, 98 (1998), pp. 211-216
[28.]
J.K. Liao, W.S. Shin, W.Y. Lee, S.L. Clark.
Oxidized low-density lipoprotein decreases the expression of endothelial nitric oxide synthase.
J Biol Chem, 270 (1995), pp. 319-324
[29.]
F. Vidal, C. Colomé, J. Martínez-González, L. Badimon.
Atherogenic concentrations of native low-density lipoproteins down-regulate nitric-oxide-synthase mRNA and protein levels in endothelial cells.
Eur J Biochem, 252 (1998), pp. 378-384
[30.]
V. Llorente, L. Badimon.
Bases celulares y moleculares de la acumulación de colesterol en la pared vascular y su contribución a la progresión de la lesión aterosclerótica.
Rev Esp Cardiol, 51 (1998), pp. 633-641
[31.]
O. Feron, C. Dessy, S. Moniotte, J.P. Desager, J.L. Balligand.
Hypercholesterolemia decreases nitric oxide production by promoting the interaction of caveolin and endothelial nitric oxide synthase.
J Clin Invest, 103 (1999), pp. 897-905
[32.]
J. Martínez-González, B. Raposo, C. Rodríguez, L. Badimon.
3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition prevents endothelial NO synthase downregulation by atherogenic levels of native LDLs. Balance between transcriptional and post-transcriptional regulation.
Arterioscler Thromb Vascular Biol, 21 (2001), pp. 804-809
[33.]
R.h. Boger, S.M. Bode-Boger, A. Szuba, P.S. Tsao, J.R. Chan, O. Tangphao, et al.
Asymmetric dimethylarginine/ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia.
Circulation, 98 (1998), pp. 1842-1847
[34.]
B.S. Oemar, M.R. Tschudi, N. Godoy, V. Brovkovich, T. Malinski, T.F. Lüscher.
Reduced endothelial nitric oxide synthase expression and production in human atherosclerosis.
Circulation, 97 (1998), pp. 2494-2498
[35.]
G. Vilahur, E. Segalés, E. Salas, L. Badimon.
Effects of a novel platelet NO-donor (LA816), aspirin, clopidogrel and combined therapy in inhibiting flow and lesion-dependent thrombosis in the porcine ex vivo model.
Circulation, 110 (2004), pp. 1686-1693
[36.]
G. Vilahur, M.I. Baldellou, E. Segalés, E. Salas, L. Badimon.
Inhibition of thrombosis by a novel platelet selective S-nitrosothiol compound without hemodynamic side effects.
Cardiovasc Res, 61 (2004), pp. 806-816
[37.]
G. Vilahur, E. Segalés, L. Casaní, L. Badimon.
A novel anti-ischemic nitric oxide donor inhibits thrombosis without modifying haemodynamic parameters.
Thrombosis Hemostasis, 91 (2004), pp. 1035-1043
[38.]
M.E. Mendelson, S. O’Neill, D. George, J. Loscalzo.
Inhibition of fibrinogen binding to human platelets by S-nitroso-N-acetylcysteine.
J Biol Chem, 265 (1990), pp. 19028-19034
[39.]
A.D. Michelson, S.E. Benoit, M.I. Furman, W.L. Breckwoldt, M.J. Rohrer, M.R. Barnard, et al.
Effects of nitric oxide/EDRF on platelet surface glycoproteins.
Am J Physiol, 29 (1996), pp. H1640-H1648
[40.]
D.N. Ku, D.P. Giddens, C.K. Zarins, S. Glagov.
Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress.
Arteriosclerosis, 5 (1985), pp. 293-302
[41.]
P.F. Davies.
Flow-mediated endothelial mechanotransduction.
Physiol Rev, 75 (1995), pp. 519-560
[42.]
J.N. Topper, J. Cai, D. Falb, M.A. Gimbrone Jr.
Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxyde synthase are selectively up-regulated by steady laminar shear stress.
Proc Natl Acad Sci USA, 93 (1996), pp. 10417-10422
[43.]
N. Resnick, H. Yahav, S. Schubert, E. Wolfovitz, A. Shay.
Signalling pathways in vascular endothelium activated by shear stress: relevance to atherosclerosis.
Curr Opin Lipidol, 11 (2000), pp. 167-177
[44.]
T. Nagel, N. Resnick, C.F. Dewey, M.A. Gimbrone Jr.
Vascular endothelial cells respond to spatial gradients in fluid shear stress by enhanced activation of transcription factors.
Arterioscler Thromb Vasc Biol, 19 (1999), pp. 1825-1834
[45.]
S. Dimmeler, C. Hermann, A.M. Zeiher.
Apoptosis of endothelial cells. Contribution to the pathophysiology of atherosclerosis.
Eur Cytokine Netw, 9 (1998), pp. 697-698
[46.]
J. Martínez-González, L. Badimon.
Reendotelización, engrosamiento intimal y remodelado vascular. ¿Un denominador común?.
Rev Esp Cardiol, 53 (2000), pp. 1425-1427
[47.]
L. Badimon, J.J. Badimon, A. Galvez, J.H. Chesebro, V. Fuster.
Influence of arterial damage and wall shear rate on platelet deposition. Ex vivo study in a swine model.
Arteriosclerosis, 6 (1986), pp. 312-320
[48.]
L. Badimon, J.H. Chesebro, J.J. Badimon.
Thrombus formation on ruptured atherosclerotic plaques and rethrombosis on evolving thrombi.
Circulation, 86 (1992), pp. III74-III85
[49.]
A. Fernández-Ortiz, J.J. Badimon, E. Falk, V. Fuster, B. Meyer, A. Mailhac, et al.
Characterization of the relative thrombogenicity of atherosclerotic plaque components: Implications for consequences of plaque rupture.
J Am Coll Cardiol, 23 (1994), pp. 1562-1569
[50.]
V. Toschi, R. Gallo, M. Lettino, J.T. Fallon, S.D. Gertz, A. Fernández-Ortiz, et al.
Tissue factor modulates the thrombogenicity of human atherosclerotic plaques.
Circulation, 95 (1997), pp. 594-599
[51.]
J.J. Badimon, M. Lettino, V. Toschi, V. Fuster, M. Berrozpe, J.H. Chesebro, et al.
Local inhibition of tissue factor reduces the thrombogenicity of disrupted human atherosclerotic plaques. Effects of TFPI on plaque thrombogenicity under flow conditions.
Circulation, 99 (1999), pp. 1780-1787
[52.]
V. Fuster, E. Falk, J.T. Fallon, L. Badimon, J.H. Chesebro, J.J. Badimon.
The three processes leading to post PTCA restenosis: dependence on the lesion substrate.
Thromb Haemostasis, 74 (1995), pp. 552-559
[53.]
J.H. Ip, V. Fuster, L. Badimon, J.J. Badimon, M.B. Taubman, J.H. Chesebro.
Syndromes of accelerated atherosclerosis: role of vascular injury and smooth muscle cell proliferation.
J Am Coll Cardiol, 15 (1990), pp. 1667-1687
[54.]
E. Van Belle, C. Bauters, T. Asahara, J.M. Isner.
Endothelial regrowth after arterial injury: from vascular repair to therapeutics.
Cardiovas Res, 38 (1998), pp. 54-68
[55.]
T. Collins.
Endothelial nuclear factor-kB and the initiation of the atherosclerotic lesion.
Lab Invest, 68 (1993), pp. 499-508
[56.]
D. Thanos, T. Maniatis.
NF-kB: a lesson in family values.
Cell, 80 (1995), pp. 529-532
[57.]
T. Bourcier, G. Sukhova, P. Libby.
The nuclear factor k-B signaling pathway participates in dysregulation of vascular smooth muscle cells in vitro and in human atherosclerosis.
J Biol Chem, 272 (1997), pp. 15817-15824
[58.]
C. Rodríguez-Sinovas, J. Martínez-González, S. Sánchez-Gómez, L. Badimon.
LDL downregulate CYP51 in vascular endothelial cells and in the arterial wall through a SREBP-2 dependent mechanism.
Circ Res, 88 (2001), pp. 268-274
[59.]
C. Rodríguez, B. Raposo, J. Martínez-González, V. Llorente-Cortés, G. Vilahur, L. Badimon.
Modulation of ERG25 expression by LDL in vascular cells.
Cardiov Res, 58 (2003), pp. 178-185
[60.]
C. Yokohama, X. Wang, M.R. Briggs, A. Admon, J. Wu, X. Hua, et al.
SREBP-1, a basic helix-loop-helix leucine zipper protein that controls transcription of the LDL receptor gene.
Cell, 75 (1993), pp. 187-197
[61.]
D. López, M.P. McLean.
Sterol regulatory element-binding protein- 1a binds to cis elements in the promoter of the rat high density lipoprotein receptor SR-B1 gene.
Endocrinology, 140 (1999), pp. 5669-5681
[62.]
W.S. Yang, S.S. Deeb.
Sp1 and Sp3 transactivate the human lipoprotein lipase gene promoter through to a CT element: synergy with the sterol regulatory element binding protein and reduced transactivation of a naturally occurring promoter variant.
J Lipid Res, 39 (1998), pp. 2054-2063
[63.]
L. Fajas, K. Schoonjans, L. Gelman, J.B. Kim, J. Najib, G. Martin, et al.
Regulation of peroxisome proliferator-activated receptor (expression by adipocyte differentiation and determination factor 1/sterol regulatory element binding protein 1: implications for adipocyte differentiation and metabolism.
Mol Cell Biol, 19 (1999), pp. 5495-5503
[64.]
P. Zimmet, K.G. Alberti, J. Shaw.
Global and societal implications of the diabetes epidemic.
Nature, 414 (2001), pp. 782-787
[65.]
A. Sjöholm, T. Nyström.
Endothelial inflammation in insulin resistance.
[66.]
S.R. Kashyap, L.J. Roman, J. Lamont, B.S. Masters, M. Bajaj, S. Suraamornkul, et al.
Insulin resistance is associated with impaired nitric oxide synthase activity in skeletal muscle of type 2 diabetic subjects.
J Clin Endocrinol Metab, 90 (2005), pp. 1100-1105
[67.]
A. Aljada, R. Saadeh, E. Assian, H. Ghanim, P. Dandona.
Insulin inhibits the expression of intercellular adhesion molecule-1 by human aortic endothelial cells through stimulation of nitric oxide.
J Clin Endocrinol Metab, 85 (2000), pp. 2572-2575
[68.]
B. Schnyder, M. Pittet, J. Durand, S. Schnyder-Candrian.
Rapid effects of glucose on the insulin signalling of endothelial NO generation and epithelial Na transport.
Am J Physiol Endocrinol Metab, 282 (2002), pp. E87-94
[69.]
S. Fichtlscherer, S. Breuer, A.M. Zeiher.
Prognostic value of systemic endothelial dysfunction in patients with acute coronary syndromes: further evidence for the existence of the «vulnerable» patient.
Circulation, 110 (2004), pp. 1926-1932

Este trabajo ha sido financiado por FIS C-03/01 RED Recava, FIS PI020361, PN SAF2003-03187, Fondos de Investigación no restringidos de MSD, Programa «Freedom to Discover» BMS y Fundación de Investigación Cardiovascular Catalana-Occidente.

Copyright © 2006. Sociedad Española de Cardiología
Idiomas
Revista Española de Cardiología

Suscríbase a la newsletter

Opciones de artículo
Herramientas
es en

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

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