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Published on: September 26, 2018

Minocycline reduces plaque size in diet induced atherosclerosis via p27(Kip1)

Khurrum Shahzad1, Madhusudhan Thati, Hongjie Wang

  • 1Internal Medicine I and Clinical Chemistry, University of Heidelberg, INF 410, 69120 Heidelberg, Germany.

Atherosclerosis
|July 2, 2011
PubMed
Abstract

Insights

Minocycline, a tetracycline derivative, reduces atherosclerosis by inhibiting vascular smooth muscle cell proliferation. This novel anti-atherosclerotic mechanism involves p27Kip1 induction, independent of its antimicrobial properties.

Area of Science:

  • Cardiovascular Research
  • Pharmacology
  • Cell Biology

Background:

  • Minocycline exhibits vasculoprotective effects beyond its antimicrobial activity, including protection against diabetic nephropathy and reduced neointima formation.
  • The impact of minocycline on primary atherogenesis, the development of atherosclerosis, remains largely unexplored.

Purpose of the Study:

  • To investigate the effect of minocycline on de novo atherogenesis in a mouse model.
  • To elucidate the cellular mechanisms underlying minocycline's potential anti-atherosclerotic properties.

Main Methods:

  • Atherogenesis was induced in ApoE-/- mice on a high-fat diet (HFD) with or without minocycline treatment.
  • Morphological and immunohistochemical analyses were performed to assess plaque development.
  • In vitro studies analyzed minocycline's effects on vascular smooth muscle cell (VSMC) proliferation, apoptosis, migration, and expression of key proteins like p27(Kip1) and PARP-1.

Main Results:

  • Minocycline treatment significantly reduced plaque size and stenosis in ApoE-/- HFD mice.
  • This reduction was associated with decreased VSMC proliferation, lower PAR modification, and increased p27(Kip1) expression within atherosclerotic plaques.
  • In vitro, minocycline inhibited VSMC proliferation by inducing p27(Kip1) and inhibiting PARP-1 and PAR modification, independent of effects on migration or apoptosis.

Conclusions:

  • Minocycline demonstrates a novel anti-atherosclerotic mechanism by inhibiting VSMC proliferation via p27(Kip1) induction.
  • These findings establish minocycline as a potential therapeutic agent for atherosclerosis, acting through a pathway distinct from its antibiotic functions.
  • The study highlights the role of p27(Kip1) in mediating minocycline's anti-proliferative effects on VSMCs during atherogenesis.

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