Buscar en
Clínica e Investigación en Arteriosclerosis
Toda la web
Inicio Clínica e Investigación en Arteriosclerosis La vitamina D induce apoptosis en células musculares lisas
Información de la revista
Vol. 13. Núm. 4.
Páginas 154-159 (Enero 2001)
Descargar PDF
Más opciones de artículo
Vol. 13. Núm. 4.
Páginas 154-159 (Enero 2001)
Acceso a texto completo
La vitamina D induce apoptosis en células musculares lisas
M.J. Gimeno1
Autor para correspondencia

Correspondencia: Departamento de Ciencias Morfológicas y Cirugía. Facultad de Medicina. Universidad de Alcalá. Ctra N-II, km 33.600. 28871 Alcalá de Henares. Madrid
, J.M. Bellón, C. Corrales, M. Rodríguez, R. López, J. Buján
Departamento de Ciencias Morfológicas y Cirugía. Facultad de Medicina. Universidad de Alcalá. Madrid
Información del artículo
Descargar PDF

La degeneración de la capa media arterial es una de las características de la arteriosclerosis que compromete tanto a las láminas elásticas como a las células musculares y a la matriz extracelular. Uno de los factores que aumentan la calcificación arterial es la vitamina D que, administrada junto a una dieta hipercolesterolémica, favorece también el depósito de colesterol y participa en el avance de la lesion vascular. El objetivo de este trabajo fue valorar el efecto de distintas concentraciones de vitamina D2 sobre la proliferación de células musculares lisas en cultivo


Se utilizaron células musculares procedentes de arteria abdominal de rata y se ensayaron distintas concentraciones de vitamina D2 (0-200.000 U/ml) durante 2 h y hasta 4 días. Se realizó un análisis de la proliferación celular en el que se valoró la incorporación de 3H-timidina y se utilizó la técnica de TUNEL para medir el daño celular como fragmentación del material genético


Las células musculares lisas del grupo control, crecidas sólo con medio de cultivo, proliferan durante todo el tiempo de estudio. Sin embargo, la presencia de esta vitamina en los medios de incubación indujo modificaciones del índice proliferativo, y se llegó a paralizar el crecimiento del cultivo con la mayor dosis de vitamina utilizada. Estos hallazgos se corresponden con un aumento de la muerte cellular por apoptosis en las mismas células


La vitamina D2 induce sobre las células musculares una inhibición de la proliferación y un aumento de la muerte cellular por apoptosis, y ambos parámetros dependen directamente del tiempo de incubación y de la concentración de vitamina D utilizada

Palabras clave:
Vitamina D
Células musculares

Degeneration of the arterial medial layer is one of the characteristic features of arteriosclerosis and affects the elastic laminae, as well as the muscle cells and extracellular matrix. Among other factors, vitamin D induces arterial calcification and when administered in combination with a high cholesterol diet, contributes to cholesterol deposition and to the advance of the vascular lesion. This study was designed to evaluate the effect of different vitamin D2 concentrations on the growth of cultured smooth muscle cells


Different vitamin D2 concentrations (0-200.000 U/ml) were applied to 2h - 4 day cultures of muscle cells from rat abdominal artery. Cell proliferation was estimated through 3Hthymidine incorporation, and cell damage, assessed as DNA fragmentation was determined using the TUNEL technique


Smooth muscle cells incubated in the absence of vitamin D2 proliferated throughout the study period. The presence of vitamin D2 in the culture medium induced changes in the proliferation rate and led to growth cessation at the highest vitamin concentration used. These findings were concurrent with an enhanced apoptosis that was noted in the same cells


Vitamin D2 inhibits the proliferation of smooth muscle cells and enhances cell death via apoptosis in a concentration- and time-dependent manner

El Texto completo está disponible en PDF
E. Rokita, T. Cichoki, D. Heck, L. Jarczyk, A. Strzalkowski.
Calcification of aortic wall in cholesterol-fed rabbit.
Atherosclerosis, 87 (1991), pp. 183-193
L.L. Demer.
Effect of calcification on in vivo mechanical response at rabbit arteries to balloon dilatation.
Circulation, 83 (1991), pp. 2083-2093
R.C. Christian, L.A. Fitzpatrick.
Vascular calcification.
Curr Opin Nephrol Hypertens, 8 (1999), pp. 443-448
R.L. Horst, J.L. Napoli, E.T. Littledike.
Discrimination in the metabolism of orally dosed ergocalciferol and cholecalciferol by the pig, rat and chick.
Biochem J, 204 (1982), pp. 185-189
H.M. Trang, D.E.C. Cole, L.A. Rubin, A. Pierratos, S. Siu, R. Vieth.
Evidence that vitamin D3 increase serum 25-hydroxyvitamin D more efficiently than does vitamin D2.
Am J Clin Nutr, 68 (1998), pp. 854-858
D.S. Rao, R. Dayal, M.L. Siu-Caldera, R.L. Horst, M.R. Uskokovic, K.Y. Tserng, et al.
Isolation and identification of 4,25-dihydroxyvitamin D2: a novel A-ring hydroxylated metabolite of vitamin D2.
J Steroid Biochem Mol Biol, 71 (1999), pp. 63-70
S. Takeo, M. Anan, K. Fujioka, T. Kajihara, S. Hiraga, K. Miyake, et al.
Functional changes of aorta with massive accumulation of calcium.
Atherosclerosis, 77 (1989), pp. 175-181
N.A. Kirui, S.E. Weisbode, O.R. Kinding.
The role of dietary calcium on the development of soft tissue mineralization due to 1,25-dihydroxy vitamin D, intoxication in rats.
Virchows Arch B, 37 (1981), pp. 251-263
N. Bennani-Kabchi, L. Kehel, F. El Bouayadi, A. Fdhil Hamarti, A. Saidi, G. Marquie.
New model of atherosclerosis in insulin resistant sand rats: hypercholesterolemia combined with D2 vitamin.
Atherosclerosis, 150 (2000), pp. 55-61
M. Mohtai, T. Yamamoto.
Smooth muscle cell proliferation in the rat coronary artery induced by vitamin D.
Atherosclerosis, 63 (1987), pp. 193-202
N. Bennani-Kabchi, L. Kehel, F. El Bouayadi, A. Amarti, A. Saidi, G. Marquie.
New model of atherosclerosis in sand rats subjected to a high cholesterol diet and vitamin D2.
Therapie, 54 (1999), pp. 559-565
W.E. Stehbens.
Localization of experimental calcification in rabbit blood vessels with particular reference to haemodynamics.
Angiology, 39 (1988), pp. 597-608
A. Kamio, T. Taguchi, M. Shirasishi, K. Shitarra, K. Fukushima, S. Takebayaschi.
Vitamin D sclerosis in rats.
Acta Pathol, 29 (1979), pp. 545-562
M. Kunitomo, K. Kinoshita, Y. Bando.
Experimental atherosclerosis in rat fed a vitamin D, colesterol-rich diet.
J Pharmacol Dyn, 4 (1981), pp. 718-723
R. Eisenstein, L. Zeruolis.
Vitamin D induced aortic calcification: a electron microscopic analysis.
Arch Pathol, 77 (1964), pp. 27-35
D.K.M. Han, C.C. Haudenschild, M.K. Hong, B.T. Tinkle, M.B. Leon, G. Lian.
Evidence for apoptosis in human atherogenesis and in rat vascular injury model.
Am J Pathol, 147 (1995), pp. 267-277
J.M. Isner, M. Kearney, S. Bortman, J. Passeri.
Apoptosis in human atherosclerosis and restenosis.
Circulation, 91 (1995), pp. 2703-2711
G. Jones, V. Byford, H.L. Makin, R. Kremer, R.H. Rice, L.A. DeGraffernried, et al.
Anti-proliferative activity and target cell catabolism of the vitamin D analog 1 alpha 24(S)-(OH)2D2 in normal and immortalized human epidermal cells.
Biochem Pharmacol, 52 (1996), pp. 133-140
M.R. Bennett, G.I. Evan, A.C. Newby.
Deregulated expression of the c-myc oncogen abolishes inhibition of proliferation of rat vascular smooth muscle cells by serum reduction, interferon gamma, heparin and cyclic nucleotide analogues and induces apoptosis.
Circ Res, 74 (1994), pp. 525-536
T.N. James.
Normal and abnormal consequences of apoptosis in the human heart from postnatal morphogenesis to paroxysmal arrhythmias.
Circulation, 90 (1994), pp. 556-573
D. Leszcynski, Y. Zhao, K. Luokkamaki, M.L. Foegh.
Apoptosis of vascular smooth muscle cells: protein kinase C and oncoprotein Bcl-2 are involved in regulation of apoptosis in non-transformed rat vascular smooth muscle cell.
Am J Pathol, 145 (1994), pp. 1265-1270
A. Negoescu, P. Lorimier, F. Labat-Moleur, C. Drouet, C. Robert, C. Guillermet, et al.
In situ apoptotic cell labeling by the TUNEL method: improvement and evaluation on cell preparations.
J Histochem Cytochem, 44 (1996), pp. 959-968
M.E. Sandgren, M. Bronnrgard, H.F. DeLuca.
Tissue distribution of the 1,25-dihydroxyvitamin D receptor in the male rat.
Biochem Biophys Res Commun, 181 (1991), pp. 611-616
H. Kawashima.
Receptor of 1,25-dihydroxyvitamin D in a vascular smooth muscle cell line derived from rat aorta.
Biochem Biophys Res Commun, 146 (1987), pp. 1-6
H.A. Pols, J.C. Birkenhager, J.A. Foeckens, J.P. Van Leeuwen.
Vitamin D: a modulator of cell proliferation and differentiation.
J Steroid Biochem Mol Biol, 37 (1990), pp. 873-876
J. Buján, J.M. Bellón, C. Sabater, F. Jurado, N. García-Honduvilla, B. Domínguez, et al.
Modifications induced by atherogenic diet in the capacity of the arterial wall in rats to respond to surgical insult.
Atherosclerosis, 122 (1996), pp. 141-152
B. Grasl-Kraupp, B. Ruttkay-Nedecky, H. Koudelka, K. Bulkowska, W. Bursch, H. Schulte.
In situ detection of fragmented DNA (TUNEL assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: a cautonary note.
Hepatology, 21 (1995), pp. 1465-1468
M.M. Kockx, J. Muhring, M.W. Knaapen, G.R. De Meyer.
RNA synthesis and splicing interferes with DNA in situ end labeling techniques used to detect apoptosis.
Am J Pathol, 152 (1998), pp. 885-888
M.M. Kockx, J. Muhring, H. Bortier, G.R. De Meyer, W. Jacob.
Biotinor digoxigenin-conjugated nucleotides bind to matrix vesicles in atherosclerotic plaques.
Am J Pathol, 148 (1996), pp. 1771-1777
M. Kanoh, G. Takemura, J. Misao, Y. Hayakawa, T. Aoyama, K. Nishigaki, et al.
Significance of myocytes with positive DNA in situ nick end-labeling (TUNEL) in hearts with dilated cardiomyopathy: not apoptosis but DNA repair.
Circulation, 99 (1999), pp. 2757-2764
Y. Makino, K. Shiraki, K. Sugimoto, T. Ito, T. Yamanaka, K. Fujikawa, et al.
Histological features of cirrhosis with hepatitis C virus for prediction of hepatocellular carcinoma development; a prospective study.
Anticancer Res, 20 (2000), pp. 3709-3715
D. Proudfoot, J.N. Skepper, L. Hegyi, M.R. Bennett, C.M. Shanahan, P.L. Weissberg.
Apoptosis regulates human vascular calcification in vitro: evidence for initiation of vascular calcification by apoptotic bodies.
Circ Res, 87 (2000), pp. 1055-1062
T.N. James, F. Terasaki, E.R. Pavlovich, A.M. Vickhert.
Apoptosis and pleomorphic micromitochondriosis in the sinus nodes surgically excised from five patients with the long QT syndrome.
J Clin Lab Med, 122 (1993), pp. 309-323
Copyright © 2001. Sociedad Española de Arteriosclerosis y Elsevier España, S.L.
Opciones de artículo
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