Interactive Effects of Omega-3 Polyunsaturated Fatty Acids and Secondhand Smoke in Mice and Human Subjects

Authors

Emily Wheeler, Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
Mary Walsh-Wilcox, Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
Meer Shah, Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
Abinash Achrekar, Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, NM USA
Joe R. Anderson, Department of Pharmacy Practice and Administrative Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
Mary K. Walker, Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA

Document Type

Article

Publication Date

2-21-2021

Abstract

Active smoking and secondhand smoke (SHS) exposure increase the risk of cardiovascular morbidity and mortality. Active smoking is associated with reduced levels of omega-3 polyunsaturated fatty acids (n-3 PUFA) and studies show that n-3 PUFA supplementation can improve smoking-induced vascular dysfunction. However, the relationship between n-3 PUFA and SHS exposure has not been studied. Fat-1 transgenic mice, which convert n-6 to n-3 PUFA, were fed diets with n-3 PUFA or without (n-6 PUFA diet), exposed to air or SHS for 4 weeks, and vasoreactivity, antioxidant indices, and omega-3 index (percent eicosapentaenoic+docosahexaenoic acids in RBC) measured. Compared to air-exposed mice, SHS enhanced aortic constriction in mice fed the n-6 PUFA diet (omega-3 index, 5.9±0.2%; mean±SE), but not in mice fed the n-3 PUFA diet (omega-3 index, 7.8±0.6%). SHS also significantly induced mRNA expression of cytochrome P4501A1, NADPH:quinone oxidoreductase, heme oxygenase-1, and angiotensinogen in adipose tissue, and increased antioxidant capacity only in mice on the n-6 PUFA diet. Notably, SHS reduced the omega-3 index by 1.0 percentage point (p=0.003), compared to air-exposed mice irrespective of diet. Additionally, we recruited human nonsmokers (NS) with and without SHS exposure (n=40) 19–40 years old and measured the omega-3 index and antioxidant capacity. In human subjects SHS exposure was associated with a significantly lower omega-3 index (NS, 4.4±1.1%; NS+SHS, 3.2±1.0%; mean±SD, p=0.002) and higher antioxidant capacity (p<0.001) than unexposed NS. Thus, SHS exposure is associated with lower levels of n-3 PUFA in mice and humans; however, an omega-3 index of ~8% in mice has vasoprotective and antioxidant properties.

Recommended Citation

Wheeler E, Walsh-Wilcox M, Shah M, Achrekar A, Anderson JR, Walker MK. Interactive Effects of Omega-3 Polyunsaturated Fatty Acids and Secondhand Smoke in Mice and Human Subjects. Cardiovasc Toxicol. 2021 Feb;21(2):115-126. doi: 10.1007/s12012-020-09601-6. Epub 2020 Aug 25. PMID: 32844369; PMCID: PMC7854812.