Related Experiment Video

Updated: May 11, 2026

Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery
09:41

Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery

Published on: December 23, 2014

Intimal hyperplasia after vascular injury is inhibited by antisense cdk 2 kinase oligonucleotides

R Morishita1, G H Gibbons, K E Ellison

  • 1Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford University School of Medicine, California 94305.

The Journal of Clinical Investigation
|April 1, 1994
PubMed

Insights

Inhibition of cell cycle enzymes cyclin-dependent kinase 2 (cdk 2) and cell division cycle 2 (cdc 2) using antisense oligodeoxynucleotides (ODN) significantly reduces neointima formation after vascular injury. A single treatment with HVJ-liposome delivered ODN provides sustained inhibition of hyperplasia.

Area of Science:

  • Molecular Biology
  • Cardiovascular Research
  • Gene Therapy

Background:

  • Balloon angioplasty injury activates cell cycle regulatory enzymes like cyclin-dependent kinase (cdk) 2 in rat carotid arteries.
  • This activation is implicated in smooth muscle cell proliferation and subsequent intimal hyperplasia.
  • Targeting these key enzymes offers a potential therapeutic strategy to inhibit post-injury vascular remodeling.

Purpose of the Study:

  • To investigate the efficacy of antisense phosphorothioate oligodeoxynucleotides (ODN) against cdk 2 kinase in inhibiting intimal hyperplasia.
  • To evaluate the combined effect of antisense ODN targeting both cdk 2 and cell division cycle 2 (cdc 2) kinases.
  • To determine the duration and localization of ODN within the vessel wall following intraluminal delivery.

Main Methods:

  • Antisense and sense phosphorothioate oligodeoxynucleotides (ODN) against cdk 2 kinase were delivered intraluminally using hemagglutinating virus of Japan (HVJ)-liposome-mediated transfer in a rat carotid artery balloon angioplasty model.
  • Specificity was confirmed by measuring mRNA levels of cdk 2 kinase.
  • FITC-labeled ODN was used to track its kinetics and localization in the vessel wall over time.

Main Results:

  • Antisense cdk 2 ODN treatment significantly inhibited neointima formation by 60% compared to controls.
  • Combined antisense treatment targeting both cdk 2 and cdc 2 kinases resulted in near-complete inhibition of neointima formation.
  • HVJ-liposome mediated delivery of ODN showed sustained fluorescence in the medial layer up to 2 weeks post-transfection.

Conclusions:

  • Targeting cell cycle regulatory genes, specifically cdk 2 and cdc 2, with antisense ODN is an effective strategy to inhibit intimal hyperplasia.
  • A single intraluminal administration of antisense ODN, delivered via HVJ-liposomes, can achieve sustained inhibition of neointima formation.
  • This approach holds promise for therapeutic interventions following vascular injury.

More Related Videos

A Rat Carotid Artery Pressure-Controlled Segmental Balloon Injury with Periadventitial Therapeutic Application06:53

A Rat Carotid Artery Pressure-Controlled Segmental Balloon Injury with Periadventitial Therapeutic Application

Published on: July 9, 2020

Development of a Murine Model for Femoral Artery Anastomotic Stenosis05:42

Development of a Murine Model for Femoral Artery Anastomotic Stenosis

Published on: April 18, 2025

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Vascular Spasm01:16

Vascular Spasm

The vascular phase, also known as vasospasm, is the initial stage of hemostasis, crucial for preventing excessive bleeding when a blood vessel is injured. After a vessel is cut, nerves in the damaged area trigger pain and other sensory impulses. Simultaneously, the smooth muscles in the vessel wall contract, resulting in a vascular spasm. This contraction reduces the vessel's diameter at the injury site, slowing or stopping blood loss through the vessel wall. Vascular spasms typically last for...