Study suggests nicotine-independent heart disease risk Electronic cigarette flavorings may damage the cells that line the blood vessels and increase cardiovascular disease risk, according to a study using human induced pluripotent stem cell–derived endothelial cells (iPSC-ECs). "The cinnamon-flavored product was the most toxic sample tested, producing strong cytotoxicity in iPSC-ECs that led to decreased cell survival, impaired angiogenic responses, and increased reactive oxygen species (ROS) levels and caspase 3/7 activity," reported Joseph C. Wu, MD, PhD, of the Stanford School of Medicine in California, and colleagues. Additionally, menthol flavoring also had strong cytotoxic effects on iPSC-ECs at a 1% dose of concentration, with or without nicotine, they stated in the Journal of the American College of Cardiology. The researchers examined the effects of e-liquid flavorings on endothelial cell viability by treating iPSC-ECs from healthy participants with dilutions from six commercially available e-liquids with varying nicotine levels. Wu told MedPage Today that the study design stems from work that led to the 2012 Nobel Prize in Physiology or Medicine, showing that the blood of adults can be converted to pluripotent stem cells that can be used to study specific cell lines. Most of the previous studies on the health impact of e-cigarette components have been limited to cytotoxicity studies using established cell lines, he explained, and the current study is the first to examine the endothelial impact of e-cigarette use using iPSC-derived endothelial cells. "You can't strip arteries from a healthy person to examine the impact of e-cigarette use," Wu said. "But you can ask [e-cigarette] users to give you 10 cc of their blood, and that blood can be used to make artery cells," he said. iPSC from healthy participants were manipulated to produce endothelial cells, and these cells were then exposed to various e-liquids with varying flavors and nicotine concentrations. The cells also exposed the cells to blood serum taken from people who had just used e-cigarettes. Exposure to e-liquids elicited various levels of oxidative stress, which has been implicated in endothelial injury, the authors reported. They further noted that the findings showed that the effects of e-liquid flavorings on endothelial function were stronger than the effects previously shown for nicotine exposure. "As e-cigarette use becomes more widespread, additional studies of their health effects become more urgent as this understanding could inform both public health policy and regulation," Wu and colleagues wrote. "Our current findings are an important first step in filling this gap by providing mechanistic insights on how e-cigarettes cause endothelial injury and dysfunction, which are important risk factors for the development of cardiovascular disease." In an accompanying editorial, Jane Freedman, MD, and Chinmay Trivedi, MD, PhD, both of the University of Massachusetts Medical School at Worcester, wrote that a "clear limitation" of the study was the reliance on a culture system. "Due to organ specific molecular heterogeneity of the vascular endothelium, it would be critical to examine effects of the various liquids in animal models. Most importantly, these in vivo models with hard endpoints after longer-term use, or after multiple uses, would allow us to determine a causal role of these liquids in cardiovascular disease," they wrote. Despite this limitation, Freedman and Trivedi said the findings clearly demonstrate "that e-liquid flavorings had stronger effects on cytotoxicity, vascular dysfunction, and angiogenesis than nicotine. Thus, in addition to harm from the nicotine, the additives are a potential source of adverse vascular health and one that is being disproportionately placed on the young." They noted that mounting data continue to show health harms for e-cigarette use, and the uptake of e-cigarettes among youth highlights the need for regulation of the products. "These observations suggest that, even without the smoke of combustible cigarette products, there may be a smoldering fire of adverse health effects," Freedman and Trivedi stated. Source
