Gene Expressions Associated with Ultrastructural Changes in Vascular Endothelium of Atherosclerotic Lesion
Attachment of the circulating monocytes to the
endothelium is the earliest detectable events during formation of
atherosclerosis. The adhesion molecules, chemokines and matrix
proteases genes were identified to be expressed in atherogenesis.
Expressions of these genes may influence structural integrity of the
luminal endothelium. The aim of this study is to relate changes in the
ultrastructural morphology of the aortic luminal surface and gene
expressions of the endothelial surface, chemokine and MMP-12 in
normal and hypercholesterolemic rabbits. Luminal endothelial
surface from rabbit aortic tissue was examined by scanning electron
microscopy (SEM) using low vacuum mode to ascertain
ultrastructural changes in development of atherosclerotic lesion. Gene
expression of adhesion molecules, MCP-1 and MMP-12 were studied
by Real-time PCR. Ultrastructural observations of the aortic luminal
surface exhibited changes from normal regular smooth intact
endothelium to irregular luminal surface including marked globular
appearance and ruptures of the membrane layer. Real-time PCR
demonstrated differentially expressed of studied genes in
atherosclerotic tissues. The appearance of ultrastructural changes in
aortic tissue of hypercholesterolemic rabbits is suggested to have
relation with underlying changes of endothelial surface molecules,
chemokine and MMP-12 gene expressions.
[1] Walski, M., Chlopicki, S., Celary-Walska, R., Frontczak-Baniewicz, M.
Ultrastructural alterations of endothelium covering advanced
atherosclerotic plaque in human carotid artery visualised by scanning
electron microscope. J Physiol Pharmacol, 53(4 Pt 1): p. 713-23, 2002.
[2] Wilhelm, M.G. and A.D. Cooper, Induction of atherosclerosis by human
chylomicron remnants: a hypothesis. J Atheroscler Thromb, 10(3): p.
132-9, 2003.
[3] Cybulsky, M.I., Lichtman, A. H., Hajra, L., Iiyama, K. Leukocyte
adhesion molecules in atherogenesis. Clin Chim Acta, 286(1-2): p. 207-
18, 1999.
[4] Fan, J. and T. Watanabe, Inflammatory reactions in the pathogenesis of
atherosclerosis. J Atheroscler Thromb, 10(2): p. 63-71, 2003.
[5] Galkina, E. and K. Ley, Vascular adhesion molecules in atherosclerosis.
Arterioscler Thromb Vasc Biol, 27(11): p. 2292-301, 2007.
[6] Kuzuya, M. and Iguchi, A. Role of matrix metalloproteinases in vascular
remodeling. J Atheroscler Thromb, 10(5): p. 275-82, 2003.
[7] Katsuda, S. and Kaji, T. Atherosclerosis and extracellular matrix. J
Atheroscler Thromb, 10(5): p. 267-74, 2003.
[8] Dollery, C.M. and Libby, P. Atherosclerosis and proteinase activation.
Cardiovasc Res, 69(3): p. 625-35, 2006.
[9] Dollery, C.M., McEwan, J.R. and Henney, A.M. Matrix
metalloproteinases and cardiovascular disease. Circ Res, 77(5): p. 863-8,
1995.
[10] Dollery, C.M., Owen, C. A., Sukhova, G. K., Krettek, A., Shapiro, S. D.,
and Libby, P. Neutrophil elastase in human atherosclerotic plaques:
production by macrophages. Circulation, 107(22): p. 2829-36, 2003.
[11] Halpert, I., Sires, U. I., Roby, J. D., Potter-Perigo, S., Wight, T. N.,
Shapiro, S. D., Welgus, H. G., Wickline, S. A., and Parks, W. C.
Matrilysin is expressed by lipid-laden macrophages at sites of potential
rupture in atherosclerotic lesions and localizes to areas of versican
deposition, a proteoglycan substrate for the enzyme. Proc Natl Acad Sci
U S A, 93(18): p. 9748-53, 1996.
[12] Libby, P. and P.M. Ridker, Inflammation and atherosclerosis: role of Creactive
protein in risk assessment. Am J Med, 116 Suppl 6A: p. 9S-16S,
2004.
[13] Zeng, B., Prasan, A., Fung, K. C., Solanki, V., Bruce, D., Freedman, S.
B. and Brieger, D. Elevated circulating levels of matrix
metalloproteinase-9 and -2 in patients with symptomatic coronary artery
disease. Intern Med J, 35(6): p. 331-5, 2005.
[14] Fan, J., Wang, X.,Wu, L.,Matsumoto, S. I.,Liang, J.,Koike, T.,Ichikawa,
T.,Sun, H.,Shikama, H.,Sasaguri, Y.,Watanabe, T. Macrophage-specific
overexpression of human matrix metalloproteinase-12 in transgenic
rabbits. Transgenic Res, 13(3): p. 261-9, 2004.
[15] Yu, Y., Koike, T., Kitajima, S., Liu, E., Morimoto, M., Shiomi, M.,
Hatakeyama, K., Asada, Y., Wang, K. Y., Sasaguri, Y., Watanabe, T.
Temporal and quantitative analysis of expression of metalloproteinases
(MMPs) and their endogenous inhibitors in atherosclerotic lesions.
Histol Histopathol, 23(12): p. 1503-16, 2008.
[16] Morgan, A.R., Rerkasem, K., Gallagher, P. J., Zhang, B., Morris, G. E.,
Calder, P. C., Grimble, R. F., Eriksson, P., McPheat, W. L., Shearman,
C. P., Ye, S. Differences in matrix metalloproteinase-1 and matrix
metalloproteinase-12 transcript levels among carotid atherosclerotic
plaques with different histopathological characteristics. Stroke, 35(6): p.
1310-5, 2004.
[17] Daley, S.J., Herderick, E. E., Cornhill, J. F., Rogers, K. A. Cholesterolfed
and casein-fed rabbit models of atherosclerosis. Part 1: Differing
lesion area and volume despite equal plasma cholesterol levels.
Arterioscler Thromb, 14(1): p. 95-104, 1994.
[18] Daley, S.J., Klemp, K. F., Guyton, J. R., Rogers, K. A. Cholesterol-fed
and casein-fed rabbit models of atherosclerosis. Part 2: Differing
morphological severity of atherogenesis despite matched plasma
cholesterol levels. Arterioscler Thromb, 14(1): p. 105-41, 1994.
[19] Aikawa, M., Rabkin, E., Okada, Y., Voglic, S. J., Clinton, S. K.,
Brinckerhoff, C. E., Sukhova, G. K., Libby, P. Lipid lowering by diet
reduces matrix metalloproteinase activity and increases collagen content
of rabbit atheroma: a potential mechanism of lesion stabilization.
Circulation, 97(24): p. 2433-44, 1998.
[20] Ozer, N.K., Negis, Y., Aytan, N., Villacorta, L., Ricciarelli, R., Zingg, J.
M., Azzi, A. Vitamin E inhibits CD36 scavenger receptor expression in
hypercholesterolemic rabbits. Atherosclerosis, 184(1): p. 15-20. 2006.
[21] Riedmuller, K., Metz, S., Bonaterra, G. A., Kelber, O., Weiser, D.,
Metz, J., Kinscherf, R. Cholesterol diet and effect of long-term
withdrawal on plaque development and composition in the thoracic aorta
of New Zealand White rabbits. Atherosclerosis, 210(2): p. 407-13, 2010.
[22] de Bruijn, W.C. and W. van Mourik, Scanning electron microscopic
observations of endothelial changes in experimentally induced
atheromatosis of rabbit aortas. Virchows Arch A Pathol Anat Histol,
365(1): p. 23-40, 1975.
[23] Brevetti, G., V. Schiano, and M. Chiariello, Endothelial dysfunction: a
key to the pathophysiology and natural history of peripheral arterial
disease? Atherosclerosis, 197(1): p. 1-11, 2008.
[24] Reidy, M.A. and D.E. Bowyer, Scanning electron microscope studies of
rabbit aortic endothelium in areas of haemodynamic stress during
induction of fatty streaks. Virchows Arch A Pathol Anat Histol, 377(3):
p. 237-48, 1978.
[25] Nitschmann, E., Berry, L., Bridge, S., Hatton, M. W., Richardson, M.,
Monagle, P., Chan, A. K., Andrew, M. Morphological and biochemical
features affecting the antithrombotic properties of the aorta in adult
rabbits and rabbit pups. Thromb Haemost, 79(5): p. 1034-40, 1998.
[26] Matsuda, J., Takahashi, S. Ohkoshi, K., Kaminaka, K., Kaminaka, S.,
Nozaki, C., Maeda, H., Tokunaga, T. Production of transgenic chimera
rabbit fetuses using somatic cell nuclear transfer. Cloning Stem Cells,
4(1): p. 9-19, 2002.
[27] Mestas, J. and K. Ley, Monocyte-endothelial cell interactions in the
development of atherosclerosis. Trends Cardiovasc Med, 18(6): p. 228-
32, 2008.
[28] Bobryshev, Y.V., Monocyte recruitment and foam cell formation in
atherosclerosis. Micron, 37(3): p. 208-22, 2006.
[29] Lu, Z.Y., Jensen, L. E., Huang, Y., Kealey, C., Blair, I. A., Whitehead,
A. S. The up-regulation of monocyte chemoattractant protein-1 (MCP-1)
in Ea.hy 926 endothelial cells under long-term low folate stress is
mediated by the p38 MAPK pathway. Atherosclerosis, 205(1): p. 48-54,
2009.
[30] Liang, J., Liu, E., Yu, Y., Kitajima, S., Koike, T., Jin, Y., Morimoto, M.,
Hatakeyama, K., Asada, Y., Watanabe, T., Sasaguri, Y., Watanabe, S.,
Fan, J. Macrophage metalloelastase accelerates the progression of
atherosclerosis in transgenic rabbits. Circulation, 113(16): p. 1993-2001,
2006.
[1] Walski, M., Chlopicki, S., Celary-Walska, R., Frontczak-Baniewicz, M.
Ultrastructural alterations of endothelium covering advanced
atherosclerotic plaque in human carotid artery visualised by scanning
electron microscope. J Physiol Pharmacol, 53(4 Pt 1): p. 713-23, 2002.
[2] Wilhelm, M.G. and A.D. Cooper, Induction of atherosclerosis by human
chylomicron remnants: a hypothesis. J Atheroscler Thromb, 10(3): p.
132-9, 2003.
[3] Cybulsky, M.I., Lichtman, A. H., Hajra, L., Iiyama, K. Leukocyte
adhesion molecules in atherogenesis. Clin Chim Acta, 286(1-2): p. 207-
18, 1999.
[4] Fan, J. and T. Watanabe, Inflammatory reactions in the pathogenesis of
atherosclerosis. J Atheroscler Thromb, 10(2): p. 63-71, 2003.
[5] Galkina, E. and K. Ley, Vascular adhesion molecules in atherosclerosis.
Arterioscler Thromb Vasc Biol, 27(11): p. 2292-301, 2007.
[6] Kuzuya, M. and Iguchi, A. Role of matrix metalloproteinases in vascular
remodeling. J Atheroscler Thromb, 10(5): p. 275-82, 2003.
[7] Katsuda, S. and Kaji, T. Atherosclerosis and extracellular matrix. J
Atheroscler Thromb, 10(5): p. 267-74, 2003.
[8] Dollery, C.M. and Libby, P. Atherosclerosis and proteinase activation.
Cardiovasc Res, 69(3): p. 625-35, 2006.
[9] Dollery, C.M., McEwan, J.R. and Henney, A.M. Matrix
metalloproteinases and cardiovascular disease. Circ Res, 77(5): p. 863-8,
1995.
[10] Dollery, C.M., Owen, C. A., Sukhova, G. K., Krettek, A., Shapiro, S. D.,
and Libby, P. Neutrophil elastase in human atherosclerotic plaques:
production by macrophages. Circulation, 107(22): p. 2829-36, 2003.
[11] Halpert, I., Sires, U. I., Roby, J. D., Potter-Perigo, S., Wight, T. N.,
Shapiro, S. D., Welgus, H. G., Wickline, S. A., and Parks, W. C.
Matrilysin is expressed by lipid-laden macrophages at sites of potential
rupture in atherosclerotic lesions and localizes to areas of versican
deposition, a proteoglycan substrate for the enzyme. Proc Natl Acad Sci
U S A, 93(18): p. 9748-53, 1996.
[12] Libby, P. and P.M. Ridker, Inflammation and atherosclerosis: role of Creactive
protein in risk assessment. Am J Med, 116 Suppl 6A: p. 9S-16S,
2004.
[13] Zeng, B., Prasan, A., Fung, K. C., Solanki, V., Bruce, D., Freedman, S.
B. and Brieger, D. Elevated circulating levels of matrix
metalloproteinase-9 and -2 in patients with symptomatic coronary artery
disease. Intern Med J, 35(6): p. 331-5, 2005.
[14] Fan, J., Wang, X.,Wu, L.,Matsumoto, S. I.,Liang, J.,Koike, T.,Ichikawa,
T.,Sun, H.,Shikama, H.,Sasaguri, Y.,Watanabe, T. Macrophage-specific
overexpression of human matrix metalloproteinase-12 in transgenic
rabbits. Transgenic Res, 13(3): p. 261-9, 2004.
[15] Yu, Y., Koike, T., Kitajima, S., Liu, E., Morimoto, M., Shiomi, M.,
Hatakeyama, K., Asada, Y., Wang, K. Y., Sasaguri, Y., Watanabe, T.
Temporal and quantitative analysis of expression of metalloproteinases
(MMPs) and their endogenous inhibitors in atherosclerotic lesions.
Histol Histopathol, 23(12): p. 1503-16, 2008.
[16] Morgan, A.R., Rerkasem, K., Gallagher, P. J., Zhang, B., Morris, G. E.,
Calder, P. C., Grimble, R. F., Eriksson, P., McPheat, W. L., Shearman,
C. P., Ye, S. Differences in matrix metalloproteinase-1 and matrix
metalloproteinase-12 transcript levels among carotid atherosclerotic
plaques with different histopathological characteristics. Stroke, 35(6): p.
1310-5, 2004.
[17] Daley, S.J., Herderick, E. E., Cornhill, J. F., Rogers, K. A. Cholesterolfed
and casein-fed rabbit models of atherosclerosis. Part 1: Differing
lesion area and volume despite equal plasma cholesterol levels.
Arterioscler Thromb, 14(1): p. 95-104, 1994.
[18] Daley, S.J., Klemp, K. F., Guyton, J. R., Rogers, K. A. Cholesterol-fed
and casein-fed rabbit models of atherosclerosis. Part 2: Differing
morphological severity of atherogenesis despite matched plasma
cholesterol levels. Arterioscler Thromb, 14(1): p. 105-41, 1994.
[19] Aikawa, M., Rabkin, E., Okada, Y., Voglic, S. J., Clinton, S. K.,
Brinckerhoff, C. E., Sukhova, G. K., Libby, P. Lipid lowering by diet
reduces matrix metalloproteinase activity and increases collagen content
of rabbit atheroma: a potential mechanism of lesion stabilization.
Circulation, 97(24): p. 2433-44, 1998.
[20] Ozer, N.K., Negis, Y., Aytan, N., Villacorta, L., Ricciarelli, R., Zingg, J.
M., Azzi, A. Vitamin E inhibits CD36 scavenger receptor expression in
hypercholesterolemic rabbits. Atherosclerosis, 184(1): p. 15-20. 2006.
[21] Riedmuller, K., Metz, S., Bonaterra, G. A., Kelber, O., Weiser, D.,
Metz, J., Kinscherf, R. Cholesterol diet and effect of long-term
withdrawal on plaque development and composition in the thoracic aorta
of New Zealand White rabbits. Atherosclerosis, 210(2): p. 407-13, 2010.
[22] de Bruijn, W.C. and W. van Mourik, Scanning electron microscopic
observations of endothelial changes in experimentally induced
atheromatosis of rabbit aortas. Virchows Arch A Pathol Anat Histol,
365(1): p. 23-40, 1975.
[23] Brevetti, G., V. Schiano, and M. Chiariello, Endothelial dysfunction: a
key to the pathophysiology and natural history of peripheral arterial
disease? Atherosclerosis, 197(1): p. 1-11, 2008.
[24] Reidy, M.A. and D.E. Bowyer, Scanning electron microscope studies of
rabbit aortic endothelium in areas of haemodynamic stress during
induction of fatty streaks. Virchows Arch A Pathol Anat Histol, 377(3):
p. 237-48, 1978.
[25] Nitschmann, E., Berry, L., Bridge, S., Hatton, M. W., Richardson, M.,
Monagle, P., Chan, A. K., Andrew, M. Morphological and biochemical
features affecting the antithrombotic properties of the aorta in adult
rabbits and rabbit pups. Thromb Haemost, 79(5): p. 1034-40, 1998.
[26] Matsuda, J., Takahashi, S. Ohkoshi, K., Kaminaka, K., Kaminaka, S.,
Nozaki, C., Maeda, H., Tokunaga, T. Production of transgenic chimera
rabbit fetuses using somatic cell nuclear transfer. Cloning Stem Cells,
4(1): p. 9-19, 2002.
[27] Mestas, J. and K. Ley, Monocyte-endothelial cell interactions in the
development of atherosclerosis. Trends Cardiovasc Med, 18(6): p. 228-
32, 2008.
[28] Bobryshev, Y.V., Monocyte recruitment and foam cell formation in
atherosclerosis. Micron, 37(3): p. 208-22, 2006.
[29] Lu, Z.Y., Jensen, L. E., Huang, Y., Kealey, C., Blair, I. A., Whitehead,
A. S. The up-regulation of monocyte chemoattractant protein-1 (MCP-1)
in Ea.hy 926 endothelial cells under long-term low folate stress is
mediated by the p38 MAPK pathway. Atherosclerosis, 205(1): p. 48-54,
2009.
[30] Liang, J., Liu, E., Yu, Y., Kitajima, S., Koike, T., Jin, Y., Morimoto, M.,
Hatakeyama, K., Asada, Y., Watanabe, T., Sasaguri, Y., Watanabe, S.,
Fan, J. Macrophage metalloelastase accelerates the progression of
atherosclerosis in transgenic rabbits. Circulation, 113(16): p. 1993-2001,
2006.
@article{"International Journal of Medical, Medicine and Health Sciences:50751", author = "M. Maimunah and G.A. Froemming and H. Nawawi and M.I. Nafeeza and O. Effat and M.R. Rohayu Izanwati and M.S. Mohamed Saifulaman", title = "Gene Expressions Associated with Ultrastructural Changes in Vascular Endothelium of Atherosclerotic Lesion", abstract = "Attachment of the circulating monocytes to the
endothelium is the earliest detectable events during formation of
atherosclerosis. The adhesion molecules, chemokines and matrix
proteases genes were identified to be expressed in atherogenesis.
Expressions of these genes may influence structural integrity of the
luminal endothelium. The aim of this study is to relate changes in the
ultrastructural morphology of the aortic luminal surface and gene
expressions of the endothelial surface, chemokine and MMP-12 in
normal and hypercholesterolemic rabbits. Luminal endothelial
surface from rabbit aortic tissue was examined by scanning electron
microscopy (SEM) using low vacuum mode to ascertain
ultrastructural changes in development of atherosclerotic lesion. Gene
expression of adhesion molecules, MCP-1 and MMP-12 were studied
by Real-time PCR. Ultrastructural observations of the aortic luminal
surface exhibited changes from normal regular smooth intact
endothelium to irregular luminal surface including marked globular
appearance and ruptures of the membrane layer. Real-time PCR
demonstrated differentially expressed of studied genes in
atherosclerotic tissues. The appearance of ultrastructural changes in
aortic tissue of hypercholesterolemic rabbits is suggested to have
relation with underlying changes of endothelial surface molecules,
chemokine and MMP-12 gene expressions.", keywords = "Ultrastructure of luminal endothelial surface,Macrophage metalloelastase (MMP-12), Real-time PCR.", volume = "6", number = "6", pages = "199-6", }
