Estrogen deficiency-induced alterations of vascular MMP-2, MT1-MMP, and TIMP-2 in ovariectomized rats

Kwok Keung Lam, Pao Yun Cheng, George Hsiao, Shu Ying Chen, Hsin Hsueh Shen, Mao Hsiung Yen, Yen Mei Lee

Research output: Contribution to journalArticle

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Abstract

Background: Matrix metalloproteinases (MMPs) activity may modulate hypertension-related accumulation of extracellular matrix (ECM) in arteries. We tested whether estrogen deficiency induces alterations of vascular collagen, MMP-2, membrane-type 1-MMP (MT1-MMP), or tissue inhibitor of metalloproteinases-2 (TIMP-2) expression in ovariectomized rats, which may be associated with postmenopausal hypertension. Methods: Estrogen deficiency was induced by ovariectomy (Ovx) in female rats. Time-course changes of aortic MMPs protein expression were evaluated. Treatment with tempol or aminoguanidine was used to examine the role of oxidative stress and nitric oxide (NO) on these changes. Results: The level of the active-form MMP-2 was markedly reduced during 1-4 weeks after Ovx, with a significant increase in collagen accumulation and increased MT1-MMP expression. Although active-form MMP-2 and collagen progressively returned to normal levels, the markedly increased collagen deposition appeared again at 8 weeks and persisted until 12 weeks, followed by induction of MMP-2 and MT1-MMP at 12 weeks. The TIMP-2 level reduced for 2 weeks after Ovx, but soon returned to normal. Treatment with 17β-estradiol (E2), tempol, or aminoguanidine for 6 weeks prevented Ovx-induced blood pressure elevation and apparently reversed the MMPs changes. Conclusions: In an initial period, E2 deficiency induces a reduction of active-form MMP-2 leading to collagen accumulation, and induction of MT1-MMP, which may be a compensatory response to degrade collagen. At a latter stage, the concurrent elevation of active-form MMP-2 and MT1-MMP expression may be adaptive responses to regulate ECM composition in the vascular wall. Oxidative stress and NO contribute to activity modulation of vascular MMPs in Ovx rats.

Original languageEnglish
Pages (from-to)27-34
Number of pages8
JournalAmerican Journal of Hypertension
Volume22
Issue number1
DOIs
Publication statusPublished - Jan 2009

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Matrix Metalloproteinase 14
Tissue Inhibitor of Metalloproteinase-2
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 2
Matrix Metalloproteinases
Blood Vessels
Estrogens
Collagen
Extracellular Matrix
Nitric Oxide
Oxidative Stress
Hypertension
Membranes
Ovariectomy
Estradiol
Arteries
Blood Pressure

ASJC Scopus subject areas

  • Internal Medicine

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Estrogen deficiency-induced alterations of vascular MMP-2, MT1-MMP, and TIMP-2 in ovariectomized rats. / Lam, Kwok Keung; Cheng, Pao Yun; Hsiao, George; Chen, Shu Ying; Shen, Hsin Hsueh; Yen, Mao Hsiung; Lee, Yen Mei.

In: American Journal of Hypertension, Vol. 22, No. 1, 01.2009, p. 27-34.

Research output: Contribution to journalArticle

Lam, Kwok Keung ; Cheng, Pao Yun ; Hsiao, George ; Chen, Shu Ying ; Shen, Hsin Hsueh ; Yen, Mao Hsiung ; Lee, Yen Mei. / Estrogen deficiency-induced alterations of vascular MMP-2, MT1-MMP, and TIMP-2 in ovariectomized rats. In: American Journal of Hypertension. 2009 ; Vol. 22, No. 1. pp. 27-34.
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abstract = "Background: Matrix metalloproteinases (MMPs) activity may modulate hypertension-related accumulation of extracellular matrix (ECM) in arteries. We tested whether estrogen deficiency induces alterations of vascular collagen, MMP-2, membrane-type 1-MMP (MT1-MMP), or tissue inhibitor of metalloproteinases-2 (TIMP-2) expression in ovariectomized rats, which may be associated with postmenopausal hypertension. Methods: Estrogen deficiency was induced by ovariectomy (Ovx) in female rats. Time-course changes of aortic MMPs protein expression were evaluated. Treatment with tempol or aminoguanidine was used to examine the role of oxidative stress and nitric oxide (NO) on these changes. Results: The level of the active-form MMP-2 was markedly reduced during 1-4 weeks after Ovx, with a significant increase in collagen accumulation and increased MT1-MMP expression. Although active-form MMP-2 and collagen progressively returned to normal levels, the markedly increased collagen deposition appeared again at 8 weeks and persisted until 12 weeks, followed by induction of MMP-2 and MT1-MMP at 12 weeks. The TIMP-2 level reduced for 2 weeks after Ovx, but soon returned to normal. Treatment with 17β-estradiol (E2), tempol, or aminoguanidine for 6 weeks prevented Ovx-induced blood pressure elevation and apparently reversed the MMPs changes. Conclusions: In an initial period, E2 deficiency induces a reduction of active-form MMP-2 leading to collagen accumulation, and induction of MT1-MMP, which may be a compensatory response to degrade collagen. At a latter stage, the concurrent elevation of active-form MMP-2 and MT1-MMP expression may be adaptive responses to regulate ECM composition in the vascular wall. Oxidative stress and NO contribute to activity modulation of vascular MMPs in Ovx rats.",
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T1 - Estrogen deficiency-induced alterations of vascular MMP-2, MT1-MMP, and TIMP-2 in ovariectomized rats

AU - Lam, Kwok Keung

AU - Cheng, Pao Yun

AU - Hsiao, George

AU - Chen, Shu Ying

AU - Shen, Hsin Hsueh

AU - Yen, Mao Hsiung

AU - Lee, Yen Mei

PY - 2009/1

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N2 - Background: Matrix metalloproteinases (MMPs) activity may modulate hypertension-related accumulation of extracellular matrix (ECM) in arteries. We tested whether estrogen deficiency induces alterations of vascular collagen, MMP-2, membrane-type 1-MMP (MT1-MMP), or tissue inhibitor of metalloproteinases-2 (TIMP-2) expression in ovariectomized rats, which may be associated with postmenopausal hypertension. Methods: Estrogen deficiency was induced by ovariectomy (Ovx) in female rats. Time-course changes of aortic MMPs protein expression were evaluated. Treatment with tempol or aminoguanidine was used to examine the role of oxidative stress and nitric oxide (NO) on these changes. Results: The level of the active-form MMP-2 was markedly reduced during 1-4 weeks after Ovx, with a significant increase in collagen accumulation and increased MT1-MMP expression. Although active-form MMP-2 and collagen progressively returned to normal levels, the markedly increased collagen deposition appeared again at 8 weeks and persisted until 12 weeks, followed by induction of MMP-2 and MT1-MMP at 12 weeks. The TIMP-2 level reduced for 2 weeks after Ovx, but soon returned to normal. Treatment with 17β-estradiol (E2), tempol, or aminoguanidine for 6 weeks prevented Ovx-induced blood pressure elevation and apparently reversed the MMPs changes. Conclusions: In an initial period, E2 deficiency induces a reduction of active-form MMP-2 leading to collagen accumulation, and induction of MT1-MMP, which may be a compensatory response to degrade collagen. At a latter stage, the concurrent elevation of active-form MMP-2 and MT1-MMP expression may be adaptive responses to regulate ECM composition in the vascular wall. Oxidative stress and NO contribute to activity modulation of vascular MMPs in Ovx rats.

AB - Background: Matrix metalloproteinases (MMPs) activity may modulate hypertension-related accumulation of extracellular matrix (ECM) in arteries. We tested whether estrogen deficiency induces alterations of vascular collagen, MMP-2, membrane-type 1-MMP (MT1-MMP), or tissue inhibitor of metalloproteinases-2 (TIMP-2) expression in ovariectomized rats, which may be associated with postmenopausal hypertension. Methods: Estrogen deficiency was induced by ovariectomy (Ovx) in female rats. Time-course changes of aortic MMPs protein expression were evaluated. Treatment with tempol or aminoguanidine was used to examine the role of oxidative stress and nitric oxide (NO) on these changes. Results: The level of the active-form MMP-2 was markedly reduced during 1-4 weeks after Ovx, with a significant increase in collagen accumulation and increased MT1-MMP expression. Although active-form MMP-2 and collagen progressively returned to normal levels, the markedly increased collagen deposition appeared again at 8 weeks and persisted until 12 weeks, followed by induction of MMP-2 and MT1-MMP at 12 weeks. The TIMP-2 level reduced for 2 weeks after Ovx, but soon returned to normal. Treatment with 17β-estradiol (E2), tempol, or aminoguanidine for 6 weeks prevented Ovx-induced blood pressure elevation and apparently reversed the MMPs changes. Conclusions: In an initial period, E2 deficiency induces a reduction of active-form MMP-2 leading to collagen accumulation, and induction of MT1-MMP, which may be a compensatory response to degrade collagen. At a latter stage, the concurrent elevation of active-form MMP-2 and MT1-MMP expression may be adaptive responses to regulate ECM composition in the vascular wall. Oxidative stress and NO contribute to activity modulation of vascular MMPs in Ovx rats.

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