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.