Zoledronate upregulates MMP-9 and-13 in rat vascular smooth muscle cells by inducing oxidative stress

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ARUN M. Z. , REEL B. , Sala-Newby G. B. , BOND M., Tsaousi A., MASKELL P., ...More

DRUG DESIGN DEVELOPMENT AND THERAPY, vol.10, pp.1453-1460, 2016 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 10
  • Publication Date: 2016
  • Doi Number: 10.2147/dddt.s103124
  • Title of Journal : DRUG DESIGN DEVELOPMENT AND THERAPY
  • Page Numbers: pp.1453-1460
  • Keywords: vascular smooth muscle cell, matrix metalloproteinase, bisphosphonate, reactive oxygen species, zoledronate, NF-KAPPA-B, GENE-EXPRESSION, ACID, BISPHOSPHONATES, MATRIX, MECHANISMS, ATHEROSCLEROSIS, PROLIFERATION, HYPERPLASIA, INHIBITION

Abstract

Background: Bisphosphonates, including zoledronate, target osteoclasts and are widely used in the treatment of osteoporosis and other bone resorption diseases, despite side effects that include damaging the stomach epithelium. Beneficial and adverse effects on other organ systems, including the cardiovascular system, have also been described and could impact on the use of bisphosphonates as therapeutic agents. Vascular smooth muscle cells (VSMCs) are major constituents of the normal vascular wall and have a key role in intimal thickening and atherosclerosis, in part by secreting MMPs that remodel the extracellular matrix and cleave cell surface proteins or secreted mediators. In this study, we investigated the effects of zoledronate on MMP expression.