Vascular Actions of Anthracycline Antibiotics

Ichiro      Wakabayashi; Klaus      Groschner

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 Ca2+ 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.

Keywords: angiogenesis, anthracyclines, antineoplastic agents, endothelin, nitric oxide, oxidative stress, vasoconstriction, vasodilation