The Far Side of Vascular Injury: Nonconventional Vasoconstrictors, DNA-targeting Agents, and Agents Toxic to Vascular Smooth Muscle.
Substances historically thought to cause direct vascular injury in laboratory animals are a heterogeneous group of toxic agents with varied mechanisms of action. Morphologically, the reviewed agents can be broadly categorized into those targeting endothelial cell (ECs) and those targeting smooth muscle cells (SMCs). Anticancer drugs, immunosuppressants, and heavy metals are targeting primarily ECs while allylamine, β-aminopropionitrile, and mitogen-activated protein kinase kinase inhibitors affect mainly SMCs. It is now recognized that the pathogenicity of some of these agents is often mediated through intermediary events, particularly vasoconstriction. There are clear similarities in the clinical and microscopic findings associated with many of these agents in animals and man, allowing the use of animal models to investigate mechanisms and pathogenesis. The molecular pathogenic mechanisms and comparative morphology in animals and humans will be reviewed.
MedImmune, Cambridge, UK guionauds@medimmune.com.
Silvia
S
Guionaud
D000818:Animals; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D057772:Vascular System Injuries / Q000139:chemically induced*; D014662:Vasoconstrictor Agents / Q000009:adverse effects*
D014662:Vasoconstrictor Agents; D004247:DNA
drug-induced; laboratory animals; molecular mechanisms; morphology; toxic; vascular injury; vasculitis