Cloning and characterization of a cDNA encoding the baboon tissue inhibitor of matrix metalloproteinase-1 (TIMP-1)

Forough, Reza; Nikkari, Seppo T.; Hasenstab, David; Lea, Holly; Clowes, Alexander W.

doi:10.1016/0378-1119(95)00343-5

Cited by 5 publications

(2 citation statements)

References 19 publications

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“…Syngeneic Fischer 344 rat smooth muscle cells were transduced in vitro with baboon TIMP-1 cDNA (LTSN cells). The preparation of the replication-defective retrovirus-encoding baboon TIMP-1 (LTSN) and the isolation and transduction of the Fischer 344 rat smooth muscle cells have been described in previous publications (26,27). The control retroviral vector (LXSN) lacks the baboon TIMP-1 cDNA (28).…”

Section: Methodsmentioning

confidence: 99%

Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model.

Allaire

Forough²,

Clowes³

et al. 1998

J. Clin. Invest.

279

202

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Section: Methodsmentioning

confidence: 99%

Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model.

Allaire

Forough²,

Clowes³

et al. 1998

J. Clin. Invest.

279

202

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“…1,10 Briefly, the left carotid was surgically exposed and a 2F balloon catheter was used to denude and injure the artery wall. Immediately after injury, a catheter was inserted into the lumen of the carotid and 10 5 SMCs were infused in the lumen and allowed to attach for 15 minutes.…”

Section: Timp-1 Overexpression In Ratmentioning

confidence: 99%

Metalloproteinase Blockade by Local Overexpression of TIMP-1 Increases Elastin Accumulation in Rat Carotid Artery Intima

Forough

Lea

Starcher

et al. 1998

ATVB

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Abstract-We have recently demonstrated that the blockade of matrix metalloproteinases by local overexpression of the intrinsic inhibitor tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) reduces intimal hyperplasia. We now report a major change in the elastin content of the intima of rat carotid arteries seeded with TIMP-1-overexpressing smooth muscle cells. To understand the mechanism responsible for elastin accumulation, synthesis and degradation of elastin in TIMP-1 and control cell-seeded rats were measured. There were no differences in elastin mRNA or elastin synthesis, as documented by 14 [C]proline incorporation between TIMP-1 and control cell-seeded arteries. In contrast, there was an increase in cross-linked elastin in the TIMP-1 group. In addition, in TIMP-1 and control rats, an elastase activity of approximately 28 kD was detected by elastin zymography and was decreased in TIMP-1 cell-seeded vessels. The 28 kD elastolytic activity was inhibited by exogenously added TIMP-1 and EDTA but not by PMSF, suggesting that it was a metalloelastase. Therefore, we have demonstrated that a shift of the proteolytic balance toward protease inhibition by TIMP-1 overexpression does not change elastin synthesis but rather changes posttranslational processing, resulting in increased elastin accumulation. 1 We now report a major change in the elastin constitution in the intima of rat carotid arteries seeded with TIMP-1-overexpressing smooth muscle cells (SMCs), as demonstrated by histochemical and biochemical analysis. To understand the mechanism responsible for elastin accumulation, we looked at changes in synthesis and degradation of elastin between TIMP-1-and control-seeded rats. There were no changes in elastin synthesis, as documented by 14 [C]proline incorporation. Similarly, there were no changes in elastin mRNA level between TIMP-1 and control cell-seeded arteries. In contrast, there was an increase in cross-linked elastin in the TIMP-1 group, as measured by desmosine content. In addition, characterization of elastolytic activities in TIMP-1 and control rats by use of elastin zymography demonstrated a metalloelastase activity of approximately 28 kD that was decreased in TIMP-1-seeded compared with control cell-seeded vessels. The 28 kD elastolytic activity was inhibited by exogenously added TIMP-1 and EDTA but not by PMSF, suggesting that it is a metalloelastase. Therefore, we have demonstrated that a shift of the proteolytic balance toward protease inhibition by TIMP-1 overexpression does not change elastin synthesis but rather changes posttranslational processing, resulting in increased elastin accumulation.Elastin is one of the major connective components of the blood vessel wall and is responsible for the elastic properties of the vessel. The mature elastin fibers have an extremely slow turnover rate, so that while elastin is rapidly synthesized in young growing vessels, newly synthesized elastin is virtually nonexistent in older, mature vessels.2 It is only during injury or other pathological condition...

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Matrix Metalloproteinases in Injured Artery

Allaire¹,

Libby

Clowes

1997

Arterial Remodeling: A Critical Factor in Restenosis

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Cloning and characterization of a cDNA encoding the baboon tissue inhibitor of matrix metalloproteinase-1 (TIMP-1)

Cited by 5 publications

References 19 publications

Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model.

Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model.

Metalloproteinase Blockade by Local Overexpression of TIMP-1 Increases Elastin Accumulation in Rat Carotid Artery Intima

Matrix Metalloproteinases in Injured Artery

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