May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Pioglitazone Increases Tissue Inhibitors of Metalloproteinase-1 in Plasma in Spontaneously Hypertensive Hyperlipidemic Rats
Author Affiliations & Notes
  • K. Suda
    Show Univ. School of Medicine, Sinagawa-Ku, Japan
    Pharmacology,
  • S. Iwai
    Show Univ. School of Medicine, Sinagawa-Ku, Japan
    Pharmacology,
  • M. Okazaki
    Show Univ. School of Medicine, Sinagawa-Ku, Japan
    Pharmacology,
  • S. Oonuma
    Pathology,
    St. Marianna Univ. School of Medicine, Kawasaki city, Japan
  • T. Kumai
    Pharmacology,
    St. Marianna Univ. School of Medicine, Kawasaki city, Japan
  • T. Ueda
    Show Univ. School of Medicine, Sinagawa-Ku, Japan
    Ophthalmology,
  • M. Tadokoro
    Pathology,
    St. Marianna Univ. School of Medicine, Kawasaki city, Japan
  • R. Koide
    Show Univ. School of Medicine, Sinagawa-Ku, Japan
    Ophthalmology,
  • S. Kobayashi
    Pharmacology,
    St. Marianna Univ. School of Medicine, Kawasaki city, Japan
  • K. Oguchi
    Show Univ. School of Medicine, Sinagawa-Ku, Japan
    Pharmacology,
  • Footnotes
    Commercial Relationships K. Suda, None; S. Iwai, None; M. Okazaki, None; S. Oonuma, None; T. Kumai, None; T. Ueda, None; M. Tadokoro, None; R. Koide, None; S. Kobayashi, None; K. Oguchi, None.
  • Footnotes
    Support High-Technology Research Center Project from the Ministry of Education, Culture, Sports, Science and Technology.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3946. doi:https://doi.org/
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    • Get Citation

      K. Suda, S. Iwai, M. Okazaki, S. Oonuma, T. Kumai, T. Ueda, M. Tadokoro, R. Koide, S. Kobayashi, K. Oguchi; Pioglitazone Increases Tissue Inhibitors of Metalloproteinase-1 in Plasma in Spontaneously Hypertensive Hyperlipidemic Rats. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3946. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: Spontaneously hypertensive hyperlipidemic rats (SHHR) are developed for the early stage model of atherosclerosis (Clin. Exp. Pharmacol. Physiol. 2003). Matrix metalloproteinase-9 (MMP-9) plays an important role in atherosclerosis and retinal degeneration, and is tightly regulated by Tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 especially inhibits MMP-9 and therefore delays the development of retinal degeneration and atherosclerosis. Pioglitazone, Peroxisome Proliferator-Activated Receptor gamma agonists, is reported to decrease MMP-9 activity in vitro, but there are few reports to study effects of Pioglitazone on TIMP-1 activity. We already showed that the increase in plasma and vitreous MMP-9 activities was suppressed by Pioglitazone treatment in high fat diets and 15% sucrose solution (HFDS) treated SHHR (2006 ARVO). In this study, we investigated effects of Pioglitazone on plasma TIMP-1 activity to study whether TIMP-1 is involved in the improvement effects of Pioglitazone on MMP-9 activity.

Methods:: Four months old male SHHR and SD rats were administered NG-nitro L-arginine methyl ester for one month, then fed HFDS ad libitum for two months, and simultaneously Pioglitazone (3mg/kg or 10mg/kg s.c.) was injected for the same terms. Plasma TIMP-1 in SHHR and SD rats were examined by reverse-gelatine zymography.

Results:: Plasma TIMP-1 activity was significantly increased in HFDS treated SHHR (HFDS-SHHR) and SD rats (HFDS-SD) compared with normal diets treated rats (Control). Plasma TIMP-1 was increased in Pioglitazone treated HFDS-SHHR in a concentration-dependent manner more than non-treated HFDS-SHHR. Whereas, there are little TIMP-1 changes between HFDS-SD and Pioglitazone treated SD rats. Plasma TIMP-1 was significantly increased in Control SD rats and HFDS-SD compared with those in SHHR, respectively.

Conclusions:: TIMP-1 was abundant in HFDS-SD compared with HFDS-SHHR, although MMP-9 activity did not significantly change between both rats. That is one of the reasons for a small vascular change in HFDS-SD compared with HFDS-SHHR. In HFDS-SHHR, Pioglitazone increased plasma TIMP-1 activity. It is suggests that Pioglitazone not only suppresses the increase in MMP-9 activity, but also induces the increase in TIMP-1 activity. Thus Pioglitazone is possible to delay the development of retinal degeneration and vascular changes.

Keywords: drug toxicity/drug effects 
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