Chronic Pod-Mod E-Cigarette Aerosol Exposure Induces Aortic Dysfunction in Hypercholesterolemic Mice: Role of Oxidative Stress and Inflammation
Abstract
Background. Electronic (e-)cigarettes are the most used tobacco product amongst youth, and adults who smoke combustible cigarettes favor e-cigarettes over approved cessations aids. Despite the lower perceived harm of vaping compared to smoking, acute inhalation of e-cigarette aerosol elicits cardiovascular responses that may lead to persistent damage when repeated over time. Methods. We exposed female hypercholesterolemic mice to either pod-mod e-cigarette aerosol or filtered air daily for 24 weeks. We assessed the long-term effects of vaping on aortic stiffness and vasoreactivity, while investigating the underlying cellular and molecular mechanisms of injury. Results. Chronic inhalation of e-cigarette aerosol triggered accumulation of inflammatory signals systemically and within aortic tissues, as well as T lymphocyte accrual in the aortic wall. Limited eNOS (endothelial nitric oxide synthase) expression and enhanced superoxide radical production curbed nitric oxide (NO) bioavailability in the aorta of mice exposed to e-cigarette aerosol despite iNOS (inducible nitric oxide synthase) induction, impairing the endothelium-dependent vasodilation (EDD) that regulates blood flow distribution. Inhalation of e-cigarette aerosol thickened and stiffened aortic tissues via collagen deposition and remodeling, hindering the storage of elastic energy and limiting the cyclic distensibility that enables the aorta to function as a pressure reservoir. These effects combined contributed to…
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