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Updated: Apr 20, 2026

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

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Regulation of mitochondrial morphology by positive feedback interaction between PKCδ and Drp1 in vascular smooth

Soyeon Lim1, Se-Yeon Lee, Hyang-Hee Seo

  • 1Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University Health System, Seodaemun-gu, Seoul, 120-752, Republic of Korea.

Journal of Cellular Biochemistry
|November 18, 2014
PubMed

Insights

Dynamin-related protein-1 (Drp1) inhibition prevents vascular smooth muscle cell proliferation and migration, offering a potential therapeutic strategy for restenosis and atherosclerosis by targeting mitochondrial dynamics.

Area of Science:

  • Mitochondrial dynamics and cell signaling in cardiovascular disease.

Background:

  • Dynamin-related protein-1 (Drp1) regulates mitochondrial fission, impacting cell proliferation.
  • Drp1's role in vascular smooth muscle cell (vSMC) responses to stimuli like Angiotensin II (Ang II) and hydrogen peroxide (H2O2) is not well understood.
  • Mdivi-1, a Drp1 inhibitor, shows potential in attenuating proliferation.

Purpose of the Study:

  • To investigate the hypothesis that Drp1 inhibition prevents vascular restenosis.
  • To elucidate the molecular mechanisms underlying Drp1's role in vSMC proliferation and migration under pathological conditions.

Main Methods:

  • In vitro assays for vSMC migration and proliferation.
  • Assessment of reactive oxygen species (ROS) production and mitochondrial membrane potential.
  • Ex vivo aortic ring assays and in vivo rat carotid artery balloon injury models.
  • Analysis of Drp1 interaction with PKCδ and downstream signaling pathways (MEK1/2-ERK1/2, MMP2).

Main Results:

  • Drp1 inhibition, specifically reducing Drp1 Ser 616 phosphorylation, attenuated Ang II/H2O2-induced vSMC proliferation and migration.
  • Drp1 inhibition mitigated excessive ROS production and preserved mitochondrial membrane potential.
  • Activated Drp1 interacted with PKCδ, leading to MEK1/2-ERK1/2 and MMP2 activation under Ang II stimulation.
  • Mdivi-1 demonstrated significant anti-proliferative and anti-migratory effects in vitro, ex vivo, and in vivo, preventing neointima formation after balloon injury.

Conclusions:

  • Drp1 plays a crucial role in pathological vSMC proliferation and migration.
  • Inhibition of Drp1, via Mdivi-1, effectively prevents vascular restenosis and neointima formation.
  • Drp1 emerges as a promising therapeutic target for treating restenosis and atherosclerosis.
Keywords:
Drp1MIGRATIONNEOINTIMAL FORMATIONPKCδPROLIFERATIONVASCULAR SMOOTH MUSCLE CELL

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