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Cell cycle in vasculoproliferative diseases: potential interventions and routes of delivery
1Division of Cardiology, University of Texas Medical Branch, Galveston, Texas, USA.
Abstract:
Atherosclerosis and restenosis of epicardial vessels are among the greatest challenges facing the clinical cardiologist, and phenotypic modulation and proliferation of smooth muscle cells are major components of the vasculoproliferative response. Proliferation is regulated by the interplay of regulatory proteins at checkpoints in the cell cycle that alter cellular growth. Activation of the cell cycle and the genetic control of its progression are final common pathways in this process. Investigators have postulated that cell-cycle inhibition using drugs and genetic or physical methods has the potential to reverse or prevent the vasculoproliferative process. The current challenge is to translate in vitro data demonstrating the efficacy of cell-cycle inhibition to clinical trials. At present, the steps that must be taken to meet this goal are (1) to design methods of delivery of these agents to specific sites, (2) to identify appropriate cellular targets to elicit cell-cycle arrest, and (3) to improve the therapeutic ratio by minimizing potential side effects. This review discusses current concepts of the cell cycle, target-regulating mechanisms, and possible interventions in vasculoproliferative diseases. We also discuss ongoing clinical trials that use antiproliferative agents in the hope of limiting the course of these diseases, as well as the promise that antiproliferative therapy holds in the coming decade.
Insights
Cell-cycle inhibition shows promise for preventing and reversing vascular proliferation in diseases like atherosclerosis. Translating these findings into clinical practice requires targeted delivery, appropriate cell targets, and minimized side effects.
Area of Science:
- Cardiovascular Medicine
- Cell Biology
- Pharmacology
Background:
- Atherosclerosis and restenosis are significant clinical challenges driven by smooth muscle cell proliferation.
- Cell cycle regulation is a key factor in controlling cellular growth and the vasculoproliferative response.
Purpose of the Study:
- To review current concepts of the cell cycle and its role in vasculoproliferative diseases.
- To discuss potential interventions, including cell-cycle inhibition, for treating these conditions.
- To examine the translation of in vitro cell-cycle inhibition data to clinical applications.
Main Methods:
- Review of current literature on cell cycle regulation and its targets.
- Discussion of drug, genetic, and physical methods for cell-cycle inhibition.
- Analysis of ongoing clinical trials involving antiproliferative agents.
Main Results:
- Cell-cycle inhibition is a potential strategy to reverse or prevent vascular proliferation.
- Key challenges include targeted delivery, identifying cellular targets, and improving the therapeutic ratio.
- Antiproliferative therapies hold significant promise for future cardiovascular disease management.
Conclusions:
- Effective clinical translation of cell-cycle inhibition requires addressing delivery, targeting, and safety.
- Further research and clinical trials are essential to harness the potential of antiproliferative therapies.
- Cell-cycle modulation represents a promising therapeutic avenue for vasculoproliferative disorders.
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