Altered expression balance of matrix metalloproteinases and their inhibitors in human carotid plaque disruption: Results of quantitative tissue analysis using real-time RT-PCR method

Takeo Higashikata, Masakazu Yamagishi, Toshio Higashi, Izumi Nagata, Koji Iihara, Susumu Miyamoto, Hatsue Ishibashi-Ueda, Noritoshi Nagaya, Takashi Iwase, Hitonobu Tomoike, Aiji Sakamoto

研究成果: ジャーナルへの寄稿記事

48 引用 (Scopus)

抄録

Background: The balance between degradation and synthesis of extracellular matrix determines its content in atherosclerotic tissue. To examine the role of expression balance of matrix metalloproteinases (MMPs) to their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) and tissue factor pathway inhibitor-2 (TFPI-2) in the development and disruption of atherosclerotic plaque, these gene expressions in human carotid plaque were quantitatively determined by real-time reverse transcription (RT)-polymerase chain reaction (PCR) method. Methods: Total RNA for cDNA synthesis was extracted from tissues in 24 patients with carotid endarterectomy. The amounts of cDNAs for MMP-1, -2, -3 and -9, TFPI-2 and TIMP-1, -2 and -3 were determined by real-time RT-PCR method, and normalized with glutaraldehyde 3-dehydrogenase. Results: In plaques, the expression MMP-1 (1.53 ± 0.25, mean ± S.E.M.), MMP-3 (1.99 ± 0.59) and MMP-9 (2.00 ± 0.51) was augmented compared to those in the adjacent control regions (0.60 ± 0.16, 0.46 ± 0.18 and 0.58 ± 0.21, respectively, p < 0.05). The expression of TFPI-2 was lower in plaques (0.32 ± 0.08) than in controls (0.94 ± 0.23, p < 0.01). Although the expression of TIMP-1 was higher in plaques (1.28 ± 0.23) than in controls (0.81 ± 0.10, p < 0.05), the indices of MMP-1/TIMP-1, MMP-3/TIMP-3 and MMP-9/TIMP-1 were still significantly higher in plaques. Interestingly, MMP-9 and the resulting MMP-9/TIMP-1 balance in plaques with disruption were significantly higher (3.36 ± 1.52 and 1.66 ± 0.12, n = 11) than those in non-disrupted plaques (1.11 ± 0.52 and 0.76 ± 0.12, n = 13, p < 0.05). Conclusion: With the decreased expression of TFPI-2, upregulation of MMPs in atherosclerotic plaque was disproportional to that of TIMPs, suggesting that imbalanced degradation and synthesis of extracellular matrix persists in advanced lesions, particularly in plaques with disruption.

元の言語英語
ページ(範囲)165-172
ページ数8
ジャーナルAtherosclerosis
185
発行部数1
DOI
出版物ステータス出版済み - 3 1 2006

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Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase Inhibitors
Reverse Transcription
Matrix Metalloproteinase 9
Matrix Metalloproteinase 1
Polymerase Chain Reaction
Tissue Inhibitor of Metalloproteinases
Matrix Metalloproteinase 3
Atherosclerotic Plaques
Matrix Metalloproteinases
Extracellular Matrix
Complementary DNA
Tissue Inhibitor of Metalloproteinase-3
Tissue Inhibitor of Metalloproteinase-2
Carotid Endarterectomy
Matrix Metalloproteinase 2
Glutaral
Oxidoreductases
Up-Regulation
RNA

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

これを引用

Altered expression balance of matrix metalloproteinases and their inhibitors in human carotid plaque disruption : Results of quantitative tissue analysis using real-time RT-PCR method. / Higashikata, Takeo; Yamagishi, Masakazu; Higashi, Toshio; Nagata, Izumi; Iihara, Koji; Miyamoto, Susumu; Ishibashi-Ueda, Hatsue; Nagaya, Noritoshi; Iwase, Takashi; Tomoike, Hitonobu; Sakamoto, Aiji.

:: Atherosclerosis, 巻 185, 番号 1, 01.03.2006, p. 165-172.

研究成果: ジャーナルへの寄稿記事

Higashikata, T, Yamagishi, M, Higashi, T, Nagata, I, Iihara, K, Miyamoto, S, Ishibashi-Ueda, H, Nagaya, N, Iwase, T, Tomoike, H & Sakamoto, A 2006, 'Altered expression balance of matrix metalloproteinases and their inhibitors in human carotid plaque disruption: Results of quantitative tissue analysis using real-time RT-PCR method', Atherosclerosis, 巻. 185, 番号 1, pp. 165-172. https://doi.org/10.1016/j.atherosclerosis.2005.05.039
Higashikata, Takeo ; Yamagishi, Masakazu ; Higashi, Toshio ; Nagata, Izumi ; Iihara, Koji ; Miyamoto, Susumu ; Ishibashi-Ueda, Hatsue ; Nagaya, Noritoshi ; Iwase, Takashi ; Tomoike, Hitonobu ; Sakamoto, Aiji. / Altered expression balance of matrix metalloproteinases and their inhibitors in human carotid plaque disruption : Results of quantitative tissue analysis using real-time RT-PCR method. :: Atherosclerosis. 2006 ; 巻 185, 番号 1. pp. 165-172.
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title = "Altered expression balance of matrix metalloproteinases and their inhibitors in human carotid plaque disruption: Results of quantitative tissue analysis using real-time RT-PCR method",
abstract = "Background: The balance between degradation and synthesis of extracellular matrix determines its content in atherosclerotic tissue. To examine the role of expression balance of matrix metalloproteinases (MMPs) to their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) and tissue factor pathway inhibitor-2 (TFPI-2) in the development and disruption of atherosclerotic plaque, these gene expressions in human carotid plaque were quantitatively determined by real-time reverse transcription (RT)-polymerase chain reaction (PCR) method. Methods: Total RNA for cDNA synthesis was extracted from tissues in 24 patients with carotid endarterectomy. The amounts of cDNAs for MMP-1, -2, -3 and -9, TFPI-2 and TIMP-1, -2 and -3 were determined by real-time RT-PCR method, and normalized with glutaraldehyde 3-dehydrogenase. Results: In plaques, the expression MMP-1 (1.53 ± 0.25, mean ± S.E.M.), MMP-3 (1.99 ± 0.59) and MMP-9 (2.00 ± 0.51) was augmented compared to those in the adjacent control regions (0.60 ± 0.16, 0.46 ± 0.18 and 0.58 ± 0.21, respectively, p < 0.05). The expression of TFPI-2 was lower in plaques (0.32 ± 0.08) than in controls (0.94 ± 0.23, p < 0.01). Although the expression of TIMP-1 was higher in plaques (1.28 ± 0.23) than in controls (0.81 ± 0.10, p < 0.05), the indices of MMP-1/TIMP-1, MMP-3/TIMP-3 and MMP-9/TIMP-1 were still significantly higher in plaques. Interestingly, MMP-9 and the resulting MMP-9/TIMP-1 balance in plaques with disruption were significantly higher (3.36 ± 1.52 and 1.66 ± 0.12, n = 11) than those in non-disrupted plaques (1.11 ± 0.52 and 0.76 ± 0.12, n = 13, p < 0.05). Conclusion: With the decreased expression of TFPI-2, upregulation of MMPs in atherosclerotic plaque was disproportional to that of TIMPs, suggesting that imbalanced degradation and synthesis of extracellular matrix persists in advanced lesions, particularly in plaques with disruption.",
author = "Takeo Higashikata and Masakazu Yamagishi and Toshio Higashi and Izumi Nagata and Koji Iihara and Susumu Miyamoto and Hatsue Ishibashi-Ueda and Noritoshi Nagaya and Takashi Iwase and Hitonobu Tomoike and Aiji Sakamoto",
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T1 - Altered expression balance of matrix metalloproteinases and their inhibitors in human carotid plaque disruption

T2 - Results of quantitative tissue analysis using real-time RT-PCR method

AU - Higashikata, Takeo

AU - Yamagishi, Masakazu

AU - Higashi, Toshio

AU - Nagata, Izumi

AU - Iihara, Koji

AU - Miyamoto, Susumu

AU - Ishibashi-Ueda, Hatsue

AU - Nagaya, Noritoshi

AU - Iwase, Takashi

AU - Tomoike, Hitonobu

AU - Sakamoto, Aiji

PY - 2006/3/1

Y1 - 2006/3/1

N2 - Background: The balance between degradation and synthesis of extracellular matrix determines its content in atherosclerotic tissue. To examine the role of expression balance of matrix metalloproteinases (MMPs) to their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) and tissue factor pathway inhibitor-2 (TFPI-2) in the development and disruption of atherosclerotic plaque, these gene expressions in human carotid plaque were quantitatively determined by real-time reverse transcription (RT)-polymerase chain reaction (PCR) method. Methods: Total RNA for cDNA synthesis was extracted from tissues in 24 patients with carotid endarterectomy. The amounts of cDNAs for MMP-1, -2, -3 and -9, TFPI-2 and TIMP-1, -2 and -3 were determined by real-time RT-PCR method, and normalized with glutaraldehyde 3-dehydrogenase. Results: In plaques, the expression MMP-1 (1.53 ± 0.25, mean ± S.E.M.), MMP-3 (1.99 ± 0.59) and MMP-9 (2.00 ± 0.51) was augmented compared to those in the adjacent control regions (0.60 ± 0.16, 0.46 ± 0.18 and 0.58 ± 0.21, respectively, p < 0.05). The expression of TFPI-2 was lower in plaques (0.32 ± 0.08) than in controls (0.94 ± 0.23, p < 0.01). Although the expression of TIMP-1 was higher in plaques (1.28 ± 0.23) than in controls (0.81 ± 0.10, p < 0.05), the indices of MMP-1/TIMP-1, MMP-3/TIMP-3 and MMP-9/TIMP-1 were still significantly higher in plaques. Interestingly, MMP-9 and the resulting MMP-9/TIMP-1 balance in plaques with disruption were significantly higher (3.36 ± 1.52 and 1.66 ± 0.12, n = 11) than those in non-disrupted plaques (1.11 ± 0.52 and 0.76 ± 0.12, n = 13, p < 0.05). Conclusion: With the decreased expression of TFPI-2, upregulation of MMPs in atherosclerotic plaque was disproportional to that of TIMPs, suggesting that imbalanced degradation and synthesis of extracellular matrix persists in advanced lesions, particularly in plaques with disruption.

AB - Background: The balance between degradation and synthesis of extracellular matrix determines its content in atherosclerotic tissue. To examine the role of expression balance of matrix metalloproteinases (MMPs) to their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) and tissue factor pathway inhibitor-2 (TFPI-2) in the development and disruption of atherosclerotic plaque, these gene expressions in human carotid plaque were quantitatively determined by real-time reverse transcription (RT)-polymerase chain reaction (PCR) method. Methods: Total RNA for cDNA synthesis was extracted from tissues in 24 patients with carotid endarterectomy. The amounts of cDNAs for MMP-1, -2, -3 and -9, TFPI-2 and TIMP-1, -2 and -3 were determined by real-time RT-PCR method, and normalized with glutaraldehyde 3-dehydrogenase. Results: In plaques, the expression MMP-1 (1.53 ± 0.25, mean ± S.E.M.), MMP-3 (1.99 ± 0.59) and MMP-9 (2.00 ± 0.51) was augmented compared to those in the adjacent control regions (0.60 ± 0.16, 0.46 ± 0.18 and 0.58 ± 0.21, respectively, p < 0.05). The expression of TFPI-2 was lower in plaques (0.32 ± 0.08) than in controls (0.94 ± 0.23, p < 0.01). Although the expression of TIMP-1 was higher in plaques (1.28 ± 0.23) than in controls (0.81 ± 0.10, p < 0.05), the indices of MMP-1/TIMP-1, MMP-3/TIMP-3 and MMP-9/TIMP-1 were still significantly higher in plaques. Interestingly, MMP-9 and the resulting MMP-9/TIMP-1 balance in plaques with disruption were significantly higher (3.36 ± 1.52 and 1.66 ± 0.12, n = 11) than those in non-disrupted plaques (1.11 ± 0.52 and 0.76 ± 0.12, n = 13, p < 0.05). Conclusion: With the decreased expression of TFPI-2, upregulation of MMPs in atherosclerotic plaque was disproportional to that of TIMPs, suggesting that imbalanced degradation and synthesis of extracellular matrix persists in advanced lesions, particularly in plaques with disruption.

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