Key Characteristics of Cardiovascular Toxicants

Abstract

Background: The concept of chemical agents having properties that confer potential hazard called key characteristics (KCs) was first developed to identify carcinogenic hazards. Identification of KCs of cardiovascular (CV) toxicants could facilitate the systematic assessment of CV hazards and understanding of assay and data gaps associated with current approaches. Objectives: We sought to develop a consensus-based synthesis of scientific evidence on the KCs of chemical and nonchemical agents known to cause CV toxicity along with methods to measure them. Methods: An expert working group was convened to discuss mechanisms associated with CV toxicity. Results: The group identified 12 KCs of CV toxicants, defined as exogenous agents that adversely interfere with function of the CV system. The KCs were organized into those primarily affecting cardiac tissue (numbers 1–4 below), the vascular system (5–7), or both (8–12), as follows: 1) impairs regulation of cardiac excitability, 2) impairs cardiac contractility and relaxation, 3) induces cardiomyocyte injury and death, 4) induces proliferation of valve stroma, 5) impacts endothelial and vascular function, 6) alters hemostasis, 7) causes dyslipidemia, 8) impairs mitochondrial function, 9) modifies autonomic nervous system activity, 10) induces oxidative stress, 11) causes inflammation, and 12) alters hormone signaling. Discussion: These 12 KCs can be used to help identify pharmaceuticals and environmental pollutants as CV toxicants, as well as to better understand the mechanistic underpinnings of their toxicity. For example, evidence exists that fine particulate matter [PM in aerodynamic diameter ( )] air pollution, arsenic, anthracycline drugs, and other exogenous chemicals possess one or more of the described KCs. In conclusion, the KCs could be used to identify potential CV toxicants and to define a set of test methods to evaluate CV toxicity in a more comprehensive and standardized manner than current approaches. https://doi.org/10.1289/EHP9321

Biochemical Evidence of PM2.5 Critical Components in the Induction of Myocardial Fibrosis in Mice

“…[14] Cytotoxicity and in ammation in cardiac tissue are critical events in CVD initiation and progression. [14][15][16][17] Furthermore, studies have indicated that water-soluble components in PM 2.5 could activate reactive oxygen species (ROS) and release in ammatory cytokines on airway epithelial cells. [18] While the literature on different PM 2.5 induces myocardial brosis is growing, it is unknown whether the PM 2.5 components at critical concentrations can target to in uence the occurrence of myocardial brosis.…”

Linking Pollutants and Therapeutics to Heart Health: Key Characteristics of Cardiovascular Toxicants

“… 5 , 6 The authors of a commentary recently published in Environmental Health Perspectives extend this work to chemicals with cardiovascular toxicity. 7 …”

“…Abnormal ion channel activity can lead to cardiac arrhythmias and sudden cardiac death. 7 Antiarrhythmic drugs 8 and the environmental chemical bisphenol A 9 are example compounds with KC1.…”

“… , which exhibits seven KCs, 7 illustrates the evolution of environmental cardiology, 19 , 20 , 21 adds Navas-Acien. Early reports of acute cardiac events requiring hospitalization on days with high exposures to were followed by studies of chronic low-level exposures.…”

“…5,6 The authors of a commentary recently published in Environmental Health Perspectives extend this work to chemicals with cardiovascular toxicity. 7 A diverse panel of 19 experts identified and grouped cardiovascular toxicants based on mechanistic similarities between therapeutics and environmental chemicals, such as air pollutants, arsenic, and lead. "We used textbook lists of drugs and chemicals that cause cardiovascular toxicity and also made a list of probable mechanisms," says Martyn Smith, a professor of toxicology at the University of California, Berkeley, and the commentary's senior author.…”