59 - Toxicology and the Endothelium

Summary

Toxic substances represent important inputs for endothelial cells (ECs). EC toxicity represents an emerging research area in the discipline of toxicology. Toxic agents can be classified as toxins of biological origin such as hormones, cytokines, and plant and animal toxins. Alternatively, toxicants are of anthropogenic origin – e.g. industrial chemicals, solvents, and polycyclic aromatic hydrocarbons. Toxicants also include naturally occurring substances released by humanactivity that aremoderately toxic or nontoxic at low levels but highly toxic when released to generate highlevels. Examples of these include metals (Hg, Cd, and Pb) and metalloids (As). Table 59–1 shows examples of toxins and toxicants that have been shownto affect the endothelium.

The endothelium is the first barrier to come into contact with toxic agents in the systemic circulation. Exposure of ECs to low levels of such substances is frequent and nonharmful. High-level exposure may lead to significant toxicity. Many agents – suchas cytokines (tumor necrosis factor [TNF]– α), drugs (antibiotics), hormones (corticosteroids, estrogens), ethanol, and trace metals – cause general damage to ECs or “endothelial dysfunction.” At that point, the endothelium loses its ability to homeostatically adapt to the toxic insult and becomes part of the resulting pathology.

Given that the structure and function of the endothelium are heterogeneous, the effects of toxins on EC phenotype may vary between different organs. Most cardiovascular pathologies can be related to endothelial toxicology, and these include coronary artery disease or atherosclerosis, arteriosclerosis, arrhythmia, hemorrhagic or thrombogenic stroke, hypertension, thrombosis, infection, and peripheral vascular disease. Some of the best-known examples are snake venoms that cause edema, hemorrhage, or thrombosis; insect toxins that cause local edema; or drug overdoses that block vasoregulation.