Effects of e.cigarettes on cardiac inflammation
The Brown lab is carrying out this project in collaboration with Dr. Laura Crotty Alexander.
Studies funded by the California Tobacco Related Disease Research Program explore the question of whether e-cig use has effects on systemic and cardiovascular inflammatory responses. Experiments take advantage of a novel system for delivering e-cigarette vapor to mice, which achieves blood nicotine levels comparable to those achieved in humans. Proposed studies use physiological, cell and molecular biological approaches to relate alterations in parasympathetic activity that occur with e-cig exposure. In particular we examine changes in the vagal cholinergic anti-inflammatory pathway and responses of α7 nicotinic ACh receptors (α7 nAChR) on macrophages to alternations in inflammatory cell function in the spleen and heart. Effects of e-cig vapor (EV) inhalation are examined at rest and in response to clinically relevant stresses imposed on the heart. We ask whether inflammation is increased in the heart at various times of e.cig vapor (EV) exposure using isolated hearts and spleen to assess tissue changes in inflammatory factors and fibrotic markers by PCR and protein arrays and macrophage infiltration by histochemistry. In these same mice we look for changes in activity of the autonomic nervous system over time, using heart rate variability is used as an index of altered parasympathetic or vagal autonomic tone and blood pressure as an indicator of changes in sympathetic tone. Isolated macrophages are also tested to determine if the cholinergic anti-inflammatory response is changed by EV exposure. Other studies examine the effects of chronic EV exposure on systemic and cardiac responses to pro-inflammatory stressors, using LPS as a general activator of systemic and cardiac inflammatory responses, and carrying out left anterior coronary artery ligation to determine infarct injury is worsened in mice exposed to EV. The overall goal is to identify a pathway (vagal cholinergic anti-inflammatory) and mechanism by which chronic e-cig exposure predisposes to cardiovascular disease.
Crotty Alexander L.E., Drummond C.A., Hepokoski M., Mathew D.P., Moshensky A., Willeford A., Das S., Singh P., Yong Z., Lee J.H., Vega K., Du A., Shin J., Javier C., Tian J., Brown J. H., Breen E.C. Chronic Inhalation of E-Cigarette Vapor Containing Nicotine Disrupts Airway Barrier Function and Induces Systemic Inflammation and Multi-Organ Fibrosis in Mice. Am J Physiol Regul Integr Comp Physiol. 2018 Jun 1;314(6):R834-R847.