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Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
Published on: January 7, 2015
Vascular actions of anthracycline antibiotics
Ichiro Wakabayashi1, Klaus Groschner
1Department of Hygiene & Preventive Medicine, School of Medicine, Yamagata University, Yamagata 990-9585, Japan. wakabaya@med.id.yamagata-u.ac.jp
Abstract:
Anthracycline antibiotics are of particular value in the therapy of malignant diseases and exert profound effects not only on tumor cells but also on cells in the cardiovascular system. These quinone drugs affect vascular tone by a multitude of mechanisms, including acute modulation of Ca(2+) homeostasis, altered expression of membrane proteins and enzymes that are involved in the control of smooth muscle contraction, and generation of autoregulatory mediators, such as nitric oxide and endothelin. Anthracyclines interfere with blood coagulation-fibrinolysis balance due to its effects on the production of prostacyclin, plasminogen activator and plasminogen activator inhibitor in the endothelium. Moreover, anthracyclines are thought to be the modulators of angiogenesis. The intensity and quality of anthracycline actions on blood vessel function are highly variable and may depend not only on the chemical structure of anthracycline but also on the type of blood vessel as well as the metabolic and redox status of the vascular tissue. Vascular actions of anthracyclines are possibly involved in both beneficial as well as toxic and undesirable side-effects such as tumor progress. Further investigations are required to clarify the relation between specific modifications of vascular cell function and clinical events observed during antineoplastic therapy with anthracyclines.
Insights
Anthracycline antibiotics impact cardiovascular cells, affecting vascular tone, blood clotting, and angiogenesis. These effects, varying by drug and vessel type, may contribute to both therapeutic benefits and toxic side effects in cancer treatment.
Area of Science:
- Cardiovascular Pharmacology
- Oncology
- Vascular Biology
Background:
- Anthracycline antibiotics are crucial in cancer therapy.
- These drugs significantly affect cardiovascular cells, not just tumor cells.
- Understanding vascular effects is key to optimizing cancer treatment.
Purpose of the Study:
- To elucidate the multifaceted mechanisms by which anthracyclines influence vascular function.
- To explore the impact of anthracyclines on vascular tone, coagulation, and angiogenesis.
- To investigate the variability in anthracycline vascular actions and their clinical implications.
Main Methods:
- Review of known mechanisms of anthracycline action on vascular cells.
- Analysis of effects on calcium homeostasis, membrane proteins, and smooth muscle contraction.
- Examination of interference with coagulation-fibrinolysis and modulation of angiogenesis.
Main Results:
- Anthracyclines modulate vascular tone via calcium homeostasis, membrane proteins, and mediators like nitric oxide and endothelin.
- These drugs disrupt the blood coagulation-fibrinolysis balance by affecting endothelial prostanoids and PAI-1.
- Anthracyclines are implicated as modulators of angiogenesis, with variable effects based on drug structure and vascular context.
Conclusions:
- Anthracycline vascular actions are complex, involving multiple pathways and influenced by drug-specific and tissue-specific factors.
- These vascular effects may underlie both beneficial outcomes and adverse events, including potential tumor progression.
- Further research is needed to correlate specific vascular cell function changes with clinical outcomes in anthracycline therapy.
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