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E-Cigs Excite the Human Splenocardiac Axis: Role of Nicotine

Institution: University of California, Los Angeles
Investigator(s): Holly Middlekauff,
Award Cycle: 2019 (Cycle 28) Grant #: 28IR-0065 Award: $935,983
Subject Area: Cardiovascular and Cerebrovascular Disease
Award Type: High Impact Research Project Award

Initial Award Abstract

“Atherosclerosis” – the process of hardening of the arteries that leads to heart attacks – is caused not only by increased cholesterol build-up, but also by inflammation in the blood vessel wall. Inflammation is a complex process that can be initiated by high adrenaline levels in the body. It has long been recognized that increased stress – both emotional and physical - can lead to high adrenaline levels and increase heart attack risk. Chronic tobacco cigarette (TC) smokers also have heightened adrenaline levels, and this may contribute to the heart attack risk associated with TC smoking. More recently, we reported that chronic electronic cigarette (EC) users also have significantly increased adrenaline levels – the critical first-step in activation inflammatory atherosclerosis. Furthermore, it is the nicotine, not the non-nicotine constituents in EC aerosol that is responsible for the acute increase in adrenaline. Of concern, using a sophisticated scan called “positron emission tomography,” we detected a significant increase in inflammation in the blood vessels in TC smokers and EC users, lending further support to the concept that ECs, like TCs, activate inflammatory atherosclerosis and may lead to heart attacks. Although EC users have increased adrenaline levels, the mechanisms underlying this increased adrenaline are unknown. In this regard, we have strong data supporting a critical role for inhaled nicotine, and not non-nicotine constituents, in increasing adrenaline levels and increasing the risk of inflammatory atherosclerosis. Nicotine receptors are present throughout the nervous system, including the brain. Chronic use of nicotine products may cause dysregulation of the regions in the brain with nicotine receptors, and lead to increased activation of nerves that carry adrenaline. Our central hypothesis is that EC use increases activation of nerves that carry adrenaline, which trigger inflammation, and that this inflammation, coupled with oxidative stress also increased in EC users, leads to blood vessel dysfunction and atherosclerosis. We will test this hypothesis, and the role of nicotine as the instigator, in the studies presented in this proposal. The results of the proposed studies will have a strong likelihood of improving the public health by determining if ECs activate the mechanisms and pathways that lead to inflammatory atherosclerosis.