Transmembrane protein 66 attenuates neointimal hyperplasia after carotid artery injury by SOCE inactivation

Jiong Yang1, Shuang Li1, Qiang Wang1

  • 1Department of Cardiology, The General Hospital of Western Theater Command, Chengdu, Sichuan 610083, P.R. China.

Insights

Transmembrane protein 66 (TMEM66) protects against neointimal hyperplasia after balloon angioplasty. Overexpression of TMEM66 inhibits vascular smooth muscle cell proliferation and migration, offering potential for restenosis treatment.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Vascular Biology

Background:

  • Neointimal hyperplasia is a major complication following balloon angioplasty.
  • Calcium signaling regulates vascular smooth muscle cell (VSMC) proliferation and migration.
  • Transmembrane protein 66 (TMEM66) is associated with store-operated calcium entry (SOCE).

Purpose of the Study:

  • To investigate the role of TMEM66 in vascular protection against balloon injury.
  • To determine if TMEM66 expression is altered after arterial injury.
  • To explore the therapeutic potential of TMEM66 in preventing neointimal hyperplasia.

Main Methods:

  • Rat balloon-induced carotid artery injury model.
  • Histological analysis for neointimal hyperplasia assessment.
  • Quantitative PCR and immunoblotting for TMEM66 expression analysis.
  • Assessment of VSMC proliferation, migration, and phenotypic markers.
  • Measurement of intracellular calcium levels ([Ca2+]i).

Main Results:

  • TMEM66 expression was decreased in injured rat carotid arteries.
  • TMEM66 overexpression attenuated neointimal hyperplasia.
  • TMEM66 overexpression inhibited VSMC proliferation and migration, restoring VSMC phenotypic markers.
  • TMEM66 overexpression reduced Stim1 and Orai1 expression and PDGF-BB-induced intracellular calcium increase.

Conclusions:

  • TMEM66 plays a protective role against balloon injury-induced neointimal hyperplasia.
  • TMEM66 modulates calcium signaling pathways involved in VSMC behavior.
  • TMEM66 represents a potential pharmacological target for treating restenosis.

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