Abstract
Inhibition of intimal hyperplasia plays an important role in preventing restenosis. Previously, we reported the provocative role of Pin1 in regulating vascular smooth muscle cell (VSMC) proliferation. Here we intended to identify whether locally delivered lentivirus-mediated siPin1 via pluronic F127 (PF127) could inhibit neointimal formation and further explore the potential mechanisms thereof. In vitro studies revealed that lentivirus-mediated siPin1 dispersed in PF127 suppressed proliferation and induced senescence in VSMCs. Reduction of Pin1 expression resulted in a decrease of phospho-Akt (p-Akt) expression level in VSMCs. Reactivation of Akt phosphorylation overcame the siPin1-mediated senescence. In a rat wire injury model, periadventitial delivery of lentivirus-mediated siPin1 via PF127 produced inhibition of intimal hyperplasia 14 days after injury without evidence for toxicity. Furthermore, the reduction of intimal thickness was associated with a decreased amount of PCNA positive cells, decreased telomerase activity and shortened telomere length. Therefore, these results suggest that PF127 delivery of lentivirus-mediated siPin1 to artery may have a therapeutic potential for the treatment of restenosis.
Keywords: Pin1, Vascular smooth muscle cell, Neointimal hyperplasia, Pluronic F127, Lentivirus.
Current Gene Therapy
Title:Prevention of Neointimal Hyperplasia by Local Application of Lentiviral Vectors Encoding Pin1 shRNA in Pluronic F127
Volume: 15 Issue: 6
Author(s): Lei Lv, Yaxue Shi, Rundan Duan, Hui Xie, Jiwei Zhang, Wei Liang, Guanhua Xue, Lan Zhang and Xiaozhong Huang
Affiliation:
Keywords: Pin1, Vascular smooth muscle cell, Neointimal hyperplasia, Pluronic F127, Lentivirus.
Abstract: Inhibition of intimal hyperplasia plays an important role in preventing restenosis. Previously, we reported the provocative role of Pin1 in regulating vascular smooth muscle cell (VSMC) proliferation. Here we intended to identify whether locally delivered lentivirus-mediated siPin1 via pluronic F127 (PF127) could inhibit neointimal formation and further explore the potential mechanisms thereof. In vitro studies revealed that lentivirus-mediated siPin1 dispersed in PF127 suppressed proliferation and induced senescence in VSMCs. Reduction of Pin1 expression resulted in a decrease of phospho-Akt (p-Akt) expression level in VSMCs. Reactivation of Akt phosphorylation overcame the siPin1-mediated senescence. In a rat wire injury model, periadventitial delivery of lentivirus-mediated siPin1 via PF127 produced inhibition of intimal hyperplasia 14 days after injury without evidence for toxicity. Furthermore, the reduction of intimal thickness was associated with a decreased amount of PCNA positive cells, decreased telomerase activity and shortened telomere length. Therefore, these results suggest that PF127 delivery of lentivirus-mediated siPin1 to artery may have a therapeutic potential for the treatment of restenosis.
Export Options
About this article
Cite this article as:
Lv Lei, Shi Yaxue, Duan Rundan, Xie Hui, Zhang Jiwei, Liang Wei, Xue Guanhua, Zhang Lan and Huang Xiaozhong, Prevention of Neointimal Hyperplasia by Local Application of Lentiviral Vectors Encoding Pin1 shRNA in Pluronic F127, Current Gene Therapy 2015; 15 (6) . https://dx.doi.org/10.2174/1566523215666151013140859
DOI https://dx.doi.org/10.2174/1566523215666151013140859 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
Call for Papers in Thematic Issues
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)
Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Protective Effect of Metformin against Oxandrolone-Induced Infertility in
Male Rats
Current Pharmaceutical Design Stroke Outcomes in Mice Lacking the Genes for Neuronal Heme Oxygenase-2 and Nitric Oxide Synthase
Current Neurovascular Research Possibility of Non-Immunosuppressive Immunophilin Ligands as Potential Therapeutic Agents for Parkinsons Disease
Current Pharmaceutical Design Lymphatic Endothelial Cells, Inflammatory Lymphangiogenesis, and Prospective Players
Current Medicinal Chemistry Stem Cells in MDR-TB and XDR - TB
Current Respiratory Medicine Reviews Salvia miltiorrhiza: A Potential Red Light to the Development of Cardiovascular Diseases
Current Pharmaceutical Design A Random Forest Model to Predict the Activity of a Large Set of Soluble Epoxide Hydrolase Inhibitors Solely Based on a Set of Simple Fragmental Descriptors
Combinatorial Chemistry & High Throughput Screening Editorial (Thematic Issue: Calcium in Heart Disease: The Ubiquitous Ion)
Medicinal Chemistry Emerging Role of NF-κB in the Pathogenesis of Hepatic Encephalopathy
Current Signal Transduction Therapy Fas Ligand Gene Therapy for Vascular Intimal Hyperplasia
Current Gene Therapy Artificial Hibernation by Phenothiazines: A Potential Neuroprotective Therapy Against Cerebral Inflammation in Stroke
Current Neurovascular Research Brown Recluse Spider Venom: Proteomic Analysis and Proposal of a Putative Mechanism of Action
Protein & Peptide Letters Novel Insights for Multiple Sclerosis and Demyelinating Disorders with Apoptosis, Autophagy, FoxO, and mTOR
Current Neurovascular Research Evaluation of Plasma Homocysteine Levels as a Prognostic Factor for the Occurrence of Perioperative Myocardial Infarction in Coronary Artery Bypass Grafting: A Pilot Study
Vascular Disease Prevention (Discontinued) Highlighting the Protective or Degenerative Role of AMPK Activators in Dementia Experimental Models
CNS & Neurological Disorders - Drug Targets Biomarkers of Subclinical Atherosclerosis and Natural Products as Complementary Alternative Medicine
Current Pharmaceutical Design Early Growth Response-1 (EGR-1) – A Key player in Myocardial Cell Injury
Cardiovascular & Hematological Agents in Medicinal Chemistry Inhibitory Effects of Flavonolignans from Silybum marianum (L.) Gaertn (Milk Thistle) on Function of Aldehyde Oxidase and Xanthine Oxidase in Rats
Letters in Drug Design & Discovery Advances on Monosaccharides and Oligosaccharides: Structural Modifications and Bioactivities
Mini-Reviews in Medicinal Chemistry Systemic Sclerosis-Related Pulmonary Hypertension: Unique Characteristics and Future Treatment Targets
Current Pharmaceutical Design