Semester

Summer

Date of Graduation

2024

Document Type

Thesis

Degree Type

MS

College

School of Medicine

Department

Exercise Physiology

Committee Chair

I. Mark Olfert

Committee Co-Chair

Paul Chantler

Committee Member

Paul Chantler

Committee Member

Elizabeth Bowdridge

Abstract

Endothelial dysfunction is a critical early marker of the pathogenesis of cardiovascular disease and a pathological biomarker in cigarette smokers. Emerging evidence finds similar cardiovascular risks resulting from electronic cigarettes (E-cig) as that seen from smoking. Logically, the time or length of exposure to E-cigs will likely influence the development of vascular dysfunction, however, the length of exposure that causes permanent damage is unknown. The goal of this study was to determine the potential window of chronic E-cig exposure that results in vascular dysfunction, which is marked by endothelial dysfunction, microvascular dysfunction, and stiffening of arteries. Based on prior chronic E-cig studies, we hypothesized it would take 16 weeks of E-cig exposure to produce vascular dysfunction in the thoracic aorta compared to age-matched controls.

C576BL/6 male and female mice at 8 weeks of age were exposed to aerosol mass concentration of 187±40 mg/m3 per day for 6-, 10-, 13-, and 16 weeks. The exposure condition was the result of 20 puffs/day (given over 1 hr with 1 puff every 3 min), 5 days/week, using 50:50 propylene glycolyl:vegetable glycerin e-liquid mix with no nicotine or flavoring and Joyetech E-cig device operating at 5-watts. At the endpoints, reactivity of the thoracic aorta was assessed using dose- response (10-9 to 10-5) to methacholine (MCh), assessing endothelial-dependent dilation (EDD), and sodium nitroprusside (SNP), assessing endothelial-independent dilation (EID), via wire myography. Ex-vivo mechanical stiffness of the aorta was also measured by assessing the force tension relationship to incremental mechanical stretch (until failure).

There was no difference between the maximal EDD in the vaped mice when compared to their age-matched air controls at any of the time points studied. The 6-week exposure had a maximal EDD of 42.28% in air mice and 62.87% in vaped mice, (p=0.15). The 10-week exposure had a maximal EDD of 69.59% in air mice and 57.00% in vaped mice, (p=0.10). The 13-week exposure had a maximal EDD of 68.60% in air mice and 63.20% in vaped mice. The 16-week exposure had a maximal EDD of 72.83% in air mice and 66.57% in vaped mice, (p=0.34). There were also no differences in EID between vaped and air controls across all time points, which was expected. Additionally, there were no differences in aortic intrinsic mechanical stiffness at the 6-, 10-, and 13-week time points. The 6-week exposure had an elastic modulus of 17.10mN/mm2 in air mice and 18.85 mN/mm2 in vaped mice, (p=0.65). The 10-week exposure had an elastic modulus of 25.18 mN/mm2 in air mice and 18.76 mN/mm2 in vaped mice, (p=0.06). The 13- week exposure had an elastic modulus of 22.82 mN/mm2 in air mice and 19.78 mN/mm2 in vaped mice, (p=0.42). There was an increase in the elastic modulus of vaped animals at the 16- week time point.The 16-week exposure had an elastic modulus of 14.95 mN/mm2 in air mice and 19.73 mN/mm2 in vaped mice, (p=0.05).

These data suggest that 16-weeks of chronic vape exposure does not produce changes in baseline endothelial dysfunction, but it may be the start of intrinsic changes toward arterial stiffness. Future studies will need to examine longer exposures to determine when the basal endothelial dysfunction is present in the thoracic aorta and if the dysfunction seen persists after vaping cessation.

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